M5 - SHARe (SNP Health Association Resource) GWAS
Investigator Names and Contact Information
Introduction/Intent
NHLBI provided funds to genotype the African American and Hispanic sub-cohort of the WHI as part of the NHLBI SNP Health Association Resource (SHARe). SHARe was initiated in 2007 to create a widely shared resource of genome-wide SNP typing and multiple phenotypes for gene discovery and replication (also known as Genome-Wide Association Studies or GWAS). See this site for more information: https://www.nhlbi.nih.gov/resources/geneticsgenomics/programs/share.htm.
The specific aims of the WHI African American and Hispanic GWAS are to:
- Enhance the statistical power for research specific to groups defined by race and ethnicity
- Discover (or replicate) genes associated with quantitative traits (such as blood pressure, blood lipids) in these groups
- Execute GWAS subset analyses interrogating potential important genetic variants and functional SNPs, individual SNPs, and haplotype-tagging SNPs in genes documented to be associated with quantitative or discrete traits in this or in other cohorts.
- Increase the number of individuals available to the research community for the construction of genetic inter-study case-control studies
The WHI GWAS was conducted in the ~13000 African American and Hispanic participants who agreed to the Supplemental Consent which allows for wide data sharing, and in deceased participants who did not withdraw their data from the study database. The genotyping center for this program was be Affymetrix. The Affymetrix 6.0 chip contains approximately 900,000 SNPs and 1 million copy number variants. Given the ethnic diversity and lower linkage disequilibrium found in African Americans, a marker density of this magnitude is necessary. A screening and replication design algorithm was used to minimize issues of multiple comparisons and identify those SNPs with the greatest power and effect for the target phenotypes. Curated, de-identified, and coded genotype and phenotype data from the SHARe projects was delivered to the National Center for Biotechnology Information (NCBI, NLM, NIH) and rapidly shared with the scientific community upon completion of quality control for genotype data and finalization of the genotype-phenotype datasets via a centralized, web-based database called dbGaP (database of genotype and phenotype). The WHI phenotype data are anticipated to cover the range of phenotypes already shared via the NHLBI Limited Access Dataset Program (BioLINCC).
Study Population
Due to funding limitations, 12,157 (8,515 African Americans and 3,642 Hispanics) of the ~ 13,000 eligible participants were selected for the SHARe GWAS. 12,007 of the DNA samples submitted were successfully genotyped and passed QC. Genetic and phenotypic data for ~8,405 African Americans and ~3,602 Hispanics are currently available on dbGaP: https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000200.v9.p3.
| Study Name (ID) | Study Population (synopsis) | Analytes | Notes |
|---|---|---|---|
| SHARe (M5) AA & H GWAS** | Selected dbGaP-eligible African American (AA) and Hispanic (H) in the OS & CT. (Not all dbGaP-eligible AA & H ppts were tested due to budget constraints.) N~12,007 (AA: N ~8,405, Hispanic: N ~3,602) See also http://www.nhlbi.nih.gov/whi/. | GWAS - Affymetrix 6.0 | GWAS and phenotype data available on dbGaP: http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000200.v9.p3 WHI phenotype data to be updated on dbGaP annually. |
M5-SHARe was included in the 2013 GWAS Imputation project (imputed to 1000G data). See the table in Key Genetics and Biomarkers Studies for information about the SHARe GWAS included in the imputition data.
Baseline clinical biomarker data (glucose, insulin, creatinine, CRP, triglycerides, cholesterol, HDL, and LDL) are available for all EA, AA, and Hispanic participants in SHARe (with sample available).
Results/Findings
For a complete, up-to-date list of WHI papers related to this ancillary study, please use the searchable Papers section of this website.
Data Dictionaries and Study Documentation
This section displays all study-related data dictionaries and study-related files. The investigators for this study will upload the datasets, data dictionaries, and other study-related files. Study-related files will be made available to the public one year after the completion of the ancillary study, with the exception of the datasets, which will only be available to those with a Data Distribution Agreement. Those will be available to those with permission to download and will appear as a download link next to the data dictionary
Data Dictionaries
Name | Description |
|---|
Study Documents
Name | Description |
|---|---|
| NameCase Control Selection Summary for SHARe.doc | Description |
Related Papers
DNA methylation-based estimator of telomere length
Telomere length (TL) is associated with several aging-related diseases. Here, we present a DNA methylation estimator of TL (DNAmTL) based on 140 CpGs. Leukocyte DNAmTL is applicable across the entire age spectrum and is more strongly associated with age than measured leukocyte TL (LTL) (r ~-0.75 for DNAmTL versus r ~ -0.35 for LTL). Leukocyte DNAmTL outperforms LTL in predicting: i) time-to-death (p=2.5E-20), ii) time-to-coronary heart disease (p=6.6E-5), iii) time-to-congestive heart failure (p...
Keywords: Dna Methylation; Leukocyte Telomere Length; Aging; Mortality; Cvd
Genome-wide association study identifies novel risk loci and provides new insights into genetic architecture of severe obesity
Keywords: Central Obesity; Hispanic American; Health Disparity; Genetics
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Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortality: Mendelian randomization
Controversy persists on the association between dairy products, especially milk, and cardiovascular diseases (CVD). Genetic proxies may improve dairy intake estimations, and clarify diet-disease relationships through Mendelian randomization. We meta-analytically (n = 20,089) evaluated associations between a lactase persistence (LP) SNP, the minichromosome maintenance complex component 6 (MCM6)-rs3754686C>T (nonpersistence>persistence), dairy intake, and CVD biomarkers in American (Hispanics, Afr...
Keywords: Mendelian Randomization; Mcm6 Genotype; Dairy Intake; Glucose; Lipids; Cardiovascular Disease; Mortality
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The impact of lifestyle habits and body weight on the risk of cardiovascular events in postmenopausal women with mild to moderate chronic kidney disease – a population based study from the Women’s health initiative
Keywords: Cardiovascular Disease; Chronic Kidney Disease; Estimated Glomerular Filtration Rate; Physical Activity; Body Mass Index; Smoking
Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids
The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. ...
Genetic loci associated with heart rate variability and their effects on cardiac disease risk
Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes p...
Genome-wide association study of lipid traits in Hispanics/Latinos: Meta-analysis
Keywords: Lipids; Cholesterol; Hispanic American; Health Disparity; Genetics
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Novel genome-wide sequence variation and susceptibility loci for cardiometabolic traits in a sub-Saharan African population
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Replication analysis of genetic variants in the WHI Hispanic cohort
Keywords: Gwas; Gallstones Disease; Complex Disorders; Admixture; Genetics
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Bayesian Variable Selection for biomarker discovery in high dimensional datasets, in the presence of error-prone self-reported outcomes
Keywords: Genetics; Self Reports; Diabetes; Bayesian Variable Selection
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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We f...
Prospective associations of C-reactive protein (CRP) levels and CRP genetic risk scores with risk of total knee and hip replacement for osteoarthritis in a diverse cohort
OBJECTIVE: To examine associations of high-sensitivity C-reactive protein (CRP) levels and polygenic CRP genetic risk scores (GRS) with risk of end-stage hip or knee osteoarthritis (OA), defined as incident total hip (THR) or knee replacement (TKR) for OA. DESIGN: This study included a cohort of postmenopausal white, African American, and Hispanic women from the Women's Health Initiative. Women were followed from baseline to date of THR or TKR, death, or December 31, 2014. Medicare claims data i...
Keywords: C-Reactive Protein; Crp; Genetic Risk Score; Inflammation; Osteoarthritis
Genome-wide association study of body fat distribution traits in Hispanics/Latinos from the HCHS/SOL
Central obesity is a leading health concern with a great burden carried by ethnic minority populations, especially Hispanics/Latinos. Genetic factors contribute to the obesity burden overall and to inter-population differences. We aimed to identify the loci associated with central adiposity measured as waist-to-hip ratio (WHR), waist circumference (WC) and hip circumference (HIP) adjusted for body mass index (adjBMI) by using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL); deter...
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucl...
Meta-analysis of genome-wide association of kidney function in individuals of African descent and Hispanics/Latinos
Keywords: Gwas; Kidney; Egfr; African Ancestry; Hispanic Ancestry
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Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-dise...
Combined associations between polygenic risk score, lifestyle risk factors and breast cancer risk
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A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry
Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we includ...
Keywords: Adiposity; Genome-Wide; Bmi; Sex-Effects
Genetic variations in magnesium-related ion channels may affect diabetes risk among African American and Hispanic American women
BACKGROUND: Prospective studies consistently link low magnesium intake to higher type 2 diabetes (T2D) risk. OBJECTIVE: We examined the association of common genetic variants [single nucleotide polymorphisms (SNPs)] in genes related to magnesium homeostasis with T2D risk and potential interactions with magnesium intake. METHODS: Using the Women's Health Initiative-SNP Health Association Resource (WHI-SHARe) study, we identified 17 magnesium-related ion channel genes (583 SNPs) and examined their...
Keywords: Transient Receptor Potential Membrane Melastatin 6 And 7 (Trpm6 And Trpm7); Polymorphism; Magnesium; Systemic Inflammation; High Sensitivity C-Reactive Protein (Hs-Crp); Interleukin-6 (Il-6); Tumor Necrosis Factor Alpha (Tnf-A); Type 2 Diabetes
Genome-wide association study of white blood cell count in 16,388 African Americans: the Continental Origins and Genetic Epidemiology Network (COGENT)
Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived ''null'' variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wi...
Keywords: None Provided
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Genome-wide trans-ethnic meta-analysis identifies seven genetic loci influencing erythrocyte traits and a role for RBPMS in erythropoiesis
Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associate...
Keywords: None Provided
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Meta-analysis of genome-wide association studies identifies genetic risk factors for stroke in African-Americans
The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African Americans, despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations.Using METAL, we conducted meta-analyses of GWAS in 14 746 African Americans (1365 ischemic ...
Keywords: Stroke; Ischemic Stroke; Gwas; Minority; African Americans; Hispanics
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Replication of breast cancer GWAS susceptibility loci in the Women's Health Initiative African American SHARe study
Genome-wide association studies (GWAS) have identified loci associated with risk of breast cancer. These studies have primarily been conducted in populations of European descent. To fully understand the impact of these loci, it is important to study groups with other genetic ancestries, including African American women.We examined 22 single-nucleotide polymorphisms (SNP), previously identified in GWAS of breast cancer risk in European and Asian descent women (index SNPs), and SNPs in the surroun...
Keywords: Genome-Wide; Breast Cancer; African American
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Genome-wide meta-analyses of smoking behaviors in African Americans
The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigare...
Keywords: Smoking; Genome-Wide Association Study; Nicotine; Genetic
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Association of DXA-derived bone mineral density and fat mass with African ancestry
Both genes and environment have been implicated in determining the complex body composition phenotypes in individuals of European ancestry; however, few studies have been conducted in other race/ethnic groups.We conducted a genome-wide admixture mapping study in an attempt to localize novel genomic regions associated with genetic ancestry.We selected a sample of 842 African-American women from the Women's Health Initiative single nucleotide polymorphism (SNP) Health Association Resource for whom...
Keywords: Admixture Mapping; Dxa; Body Composition; Fat Mass; Gwas; Lean Mass; African American; Hispanic
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Genome-wide association study (GWAS) and genome-wide by environment interaction study (GWEIS) of depressive symptoms in African American and Hispanic/Latina women
BACKGROUND: Genome-wide association studies (GWAS) have made little progress in identifying variants linked to depression. We hypothesized that examining depressive symptoms and considering gene-environment interaction (GxE) might improve efficiency for gene discovery. We therefore conducted a GWAS and genome-wide by environment interaction study (GWEIS) of depressive symptoms. METHODS: Using data from the SHARe cohort of the Women's Health Initiative, comprising African Americans (n = 7,179) an...
Keywords: Gwas; Genotype-Environment Interaction; Stressful Life Events; Social Support; Hormone Replacement Therapy; Depression
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The impact of ancestry and common genetic variants on QT interval in African Americans
Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval.First, individual estimates of African and E...
Keywords: Electrocardiogram; Ventricular Repolarization; Genome-Wide Association
Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: A genome-wide association study of 13,372 participants
Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans.To identify novel genetic variants associated with resting heart rate in African Americans.Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide geno...
Keywords: Electrocardiogram; Heart Rate Variability; Genome-Wide Association
Genetic variation predicts serum lycopene concentrations in a multiethnic population of postmenopausal women
The consumption and blood concentrations of lycopene are both positively and inversely associated with the risk of several chronic diseases. The inconsistences in lycopene disease association studies may stem from a lack of knowledge about the genetic variation in the synthesis, metabolism, and deposition of transport and binding proteins, which potentially influence serum lycopene concentrations.We examined the association between variation across the genome and serum concentrations of lycopene...
Keywords: None Provided
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Adiponectin pathway polymorphisms and risk of breast cancer in African Americans and Hispanics in the Women’s Health Initiative
Adiponectin, a protein secreted by the adipose tissue, is an endogenous insulin sensitizer with circulating levels that are decreased in obese and diabetic subjects. Recently, circulating levels of adiponectin have been correlated with breast cancer risk. Our previous work showed that polymorphisms of the adiponectin pathway are associated with breast cancer risk. We conducted the first study of adiponectin pathways in African Americans and Hispanics in the Women's Health Initiative SNP Health A...
Keywords: Adiponectin; Adipoq; Adipor1; Adipor2; Breast Cancer; Colon Cancer; Endometrial Cancer
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Trans-ethnic meta-analysis and functional annotation illuminates the genetic architecture of fasting glucose and insulin
Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta...
Keywords: Genome-Wide Association; Post-Menopausal Women; Ethnicity
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A gene-centric association scan for Coagulation Factor VII levels in European and African Americans: the Candidate Gene Association Resource (CARe) Consortium
Polymorphisms in several distinct genomic regions, including the F7 gene, were recently associated with factor VII (FVII) levels in European Americans (EAs). The genetic determinants of FVII in African Americans (AAs) are unknown. We used a 50,000 single nucleotide polymorphism (SNP) gene-centric array having dense coverage of over 2,000 candidate genes for cardiovascular disease (CVD) pathways in a community-based sample of 16,324 EA and 3898 AA participants from the Candidate Gene Association ...
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A genome-wide association study meta-analysis of clinical fracture in 10,012 African American women
BACKGROUND: Osteoporosis is a major public health problem associated with excess disability and mortality. It is estimated that 50-70% of the variation in osteoporotic fracture risk is attributable to genetic factors. The purpose of this hypothesis-generating study was to identify possible genetic determinants of fracture among African American (AA) women in a GWAS meta-analysis. METHODS: Data on clinical fractures (all fractures except fingers, toes, face, skull or sternum) were analyzed among ...
Keywords: Osteoporosis; Fracture; Minority Women; Race/Ethnicity; Genetic; Genes; Snps
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Genome-wide association and admixture analysis of glaucoma in the Women's Health Initiative
We report a genome-wide association study (GWAS) and admixture analysis of glaucoma in 12 008 African-American and Hispanic women (age 50-79 years) from the Women's Health Initiative (WHI). Although GWAS of glaucoma have been conducted on several populations, this is the first to look at glaucoma in individuals of African-American and Hispanic race/ethnicity. Prevalent and incident glaucoma was determined by self-report from study questionnaires administered at baseline (1993-1998) and annually ...
Keywords: Ancestry; Admixture; Association; Eye Disease; Glaucoma; African American; Latino American
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Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease
Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation.We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and...
Keywords: Fibrinogen; Postmenopausal; Genetic Variation; African American; Hispanic
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A meta-analysis and genome-wide association study of platelet count and mean platelet volume in African Americans
Several genetic variants associated with platelet count and mean platelet volume (MPV) were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS) enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were...
Keywords: None Provided
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Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource (CARe) Study
The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure ...
Keywords: Genetics; African Americans; Blood Pressure; Hypertension
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Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans
The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten ...
Ancestry and admixture in African American women from the Women’s Health Initiative
Keywords: Ancestry; Admixture; Stratification; Ses; African Americans
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African American race but not genome-wide ancestry is negatively associated with atrial fibrillation among postmenopausal women in the Women's Health Initiative
Atrial fibrillation (AF) is the most common arrhythmia in women and is associated with higher rates of stroke and death. Rates of AF are lower in African American subjects compared with European Americans, suggesting European ancestry could contribute to AF risk.The Women's Health Initiative (WHI) Observational Study (OS) followed up 93,676 women since the mid 1990s for various cardiovascular outcomes including AF. Multivariate Cox hazard regression analysis was used to measure the association b...
Keywords: Admixture; Association; Cardiovascular Disease; Atrial Fibrillation; Arrhythmia; Gene-Environment Interaction; African Americans; Latino Americans
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Variation in vitamin D-associated genes, cardiovascular disease, and intermediate cardiovascular phenotypes in African Americans
Keywords: Vitamin D Variants; Cardiovascular Disease; African Americans
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Genetic variants associated with height in Hispanic women in the Women’s Health Initiative Study
Keywords: Adult Height; Gwas; Admixture; Hispanics
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Replication of association of bone mineral density measures with UGT2B17 and VPS13B copy number variation in the WHI SHARe population
Keywords: Dxa; Body Composition; Bone Mineral Density; Bone Geometry; Copy Number Variation; Ugt2b17; Vps13b; African Americans; Hispanics
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Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes
Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases a...
Keywords: Diabetes Mellitus; Gwas; Gene-Gene; Gene-Diet Interaction; Family History Of Diabetes; Extreme Phenotypes
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Genome-wide association of weight change among minority women: The WHI Study
Keywords: Weight; Weight Change; Genome-Wide; Sex-Effects
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Replication study of genome-wide association study findings of longevity in white, African-American, and Hispanic women: The Women’s Health Initiative
Keywords: Gene; Genome; Healthy Aging; Exceptional Longevity; Snps
Genome-wide association of kidney function traits in post-menopausal women of varying ethnicity
Keywords: None Provided
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Genetic variants in sex hormone pathways and the risk of type 2 diabetes among African-American, Hispanic-American, and European-American postmenopausal women in the United States
BACKGROUND: Sex hormones are implicated in diabetes development. However, whether genetic variations in sex hormone pathways (SHPs) contribute to type 2 diabetes (T2D) risk remains to be delineated. We investigated the associations between genetic variations in all candidate genes in SHPs and T2D risk among a cohort of women who participated in the Women's Health Initiative (WHI). METHODS: We comprehensively examined single nucleotide polymorphisms (SNPs) located within 30 kb upstream and 30 kb ...
Keywords: Sex Hormones; Estrogen; Estrogen Receptor (Er)A; Erß; Androgen; Androgen Receptor (Ar); Cyp17; Cyp19; Sex Hormone-Binding Globulin (Shbg); And Type 2 Diabetes
GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes previously identified loci and identifies population-specific signals
QT interval prolongation is a heritable risk factor for ventricular arrhythmias and can predispose to sudden death. Most genome-wide association studies (GWAS) of QT were performed in European ancestral populations, leaving other groups uncharacterized. Herein we present the first QT GWAS of Hispanic/Latinos using data on 15,997 participants from four studies. Study-specific summary results of the association between 1000 Genomes Project (1000G) imputed SNPs and electrocardiographically measured...
Keywords: Ecg; Qt Interval; Gwas
Genome-wide association study and meta-analysis identify loci associated with ventricular and supraventricular ectopy
The genetic basis of supraventricular and ventricular ectopy (SVE, VE) remains largely uncharacterized, despite established genetic mechanisms of arrhythmogenesis. To identify novel genetic variants associated with SVE/VE in ancestrally diverse human populations, we conducted a genome-wide association study of electrocardiographically identified SVE and VE in five cohorts including approximately 43,000 participants of African, European and Hispanic/Latino ancestry. In thirteen ancestry-stratifie...
Keywords: Electrocardiogram; Ventricular Ectopy; Genome-Wide Association
Genetic variants associated with quantitative glucose homeostasis traits translate to Type 2 Diabetes in Mexican Americans: the GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium
Insulin sensitivity, insulin secretion, insulin clearance, and glucose effectiveness exhibit strong genetic components, although few studies have examined their genetic architecture or influence on type 2 diabetes (T2D) risk. We hypothesized that loci affecting variation in these quantitative traits influence T2D. We completed a multicohort genome-wide association study to search for loci influencing T2D-related quantitative traits in 4,176 Mexican Americans. Quantitative traits were measured by...
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Genome-wide association study of age at menarche in African-American women
African-American (AA) women have earlier menarche on average than women of European ancestry (EA), and earlier menarche is a risk factor for obesity and type 2 diabetes among other chronic diseases. Identification of common genetic variants associated with age at menarche has a potential value in pointing to the genetic pathways underlying chronic disease risk, yet comprehensive genome-wide studies of age at menarche are lacking for AA women. In this study, we tested the genome-wide association ...
Keywords: Age Of Menarche; Genome-Wide Association; Replication Of Candidate Genes
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Genome-wide association of urinary incontinence in post-menopausal women
Keywords: Urinary Incontinence; Genome-Wide Association; Post-Menopausal Women
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Genome-wide association of blood pressure and hypertension: the WHI study
Keywords: Blood Pressure; Hypertension; Genome-Wide Association; Candidate Gene Association
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Genome-wide association study of optimism and cynical hostility among minorities in the Women’s Health Initiative (WHI)
Keywords: Gwas; Psychological Attitudes; Optimism; Pessimism; Cynical Hostility
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Genome-wide association of kidney stones in post-menopausal women of varying ethnicity
Keywords: Kidney Stones; Genome-Wide Association; Post-Menopausal Women
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Genome-wide association analysis of coronary heart disease in WHI minorities
Keywords: Coronary Heart Disease; Genetics; Gwas; African-American; Hispanic
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Genetic variants associated with habitual physical activity
Keywords: Physical Activity; Trajectory; Genetic Variants
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Associations of genetic variation with dietary intake in WHI Minorities
Keywords: Genome-Wide; Diet; Dietary Patterns; African-American; Hispanic
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Association between vitamin D-associated genes, cancer incidence, and intermediate cancer phenotypes in African Americans
Keywords: Vitamin D-Related Genes; Cancer Incidence; African Americans
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Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network
Laboratory red blood cell (RBC) measurements are clinically important, heritable and differ among ethnic groups. To identify genetic variants that contribute to RBC phenotypes in African Americans (AAs), we conducted a genome-wide association study in up to ~16 500 AAs. The alpha-globin locus on chromosome 16pter [lead SNP rs13335629 in ITFG3 gene; P < 1E-13 for hemoglobin (Hgb), RBC count, mean corpuscular volume (MCV), MCH and MCHC] and the G6PD locus on Xq28 [lead SNP rs1050828; P < 1E - 13 f...
Keywords: Hemoglobin; Anemia; Postmenopausal; Genetic Variation; African American; Hispanic
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Gene-environment interactions and obesity traits among postmenopausal African-American and Hispanic women in the Women’s Health Initiative SHARe Study
Genome-wide association studies (GWAS) of obesity measures have identified associations with single nucleotide polymorphisms (SNPs). However, no large-scale evaluation of gene-environment interactions has been performed. We conducted a search of gene-environment (G × E) interactions in post-menopausal African-American and Hispanic women from the Women's Health Initiative SNP Health Association Resource GWAS study. Single SNP linear regression on body mass index (BMI) and waist-to-hip circumferen...
Keywords: Epistasis; Gene-Gene Interaction; Gene-Environment Interaction; Obesity; Mdr; Genome-Wide
Related Studies: M5
Admixture mapping of BMI in Hispanic and African American women: the WHI SHARe study
Keywords: Admixture Mapping; Bmi; Adiposity; Ancestry
Related Studies: M5
Genome-wide association of venous thromboembolism in African American populations
Keywords: Venous Thromboembolism; Genome-Wide; Deep Vein Thrombosis; Pulmonary Embolism
Related Studies: M5
Fifteen genetic loci associated with the electrocardiographic P wave
BACKGROUND: The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave ter...
Keywords: Electrocardiogram; Genome-Wide Association; Minority
GWAS analysis for genetic predictors of sarcopenia among WHI women enrolled in the DXA cohort
Keywords: Sarcopenia; Genome-Wide Association Studies (Gwas); African American; Hispanic; Older Women
Related Studies: M5
Sex hormone-related gene variants and cardiovascular disease in African American women
Keywords: Sex Steroid Hormone; Genome-Wide Association Study; Cardiovascular Disease; Postmenopausal Women; African American; Hispanic
Related Studies: M5
Genome-wide association study of obesity and insulin resistance-related traits in postmenopausal African-American and Hispanic women
Keywords: Body Mass Index; Obesity; Postmenopausal Women; Metabolic Syndrome; Insulin Resistance; Genome-Wide Association Study
Related Studies: M5
Shared molecular pathways and gene networks for cardiovascular disease and type 2 diabetes mellitus in women across diverse ethnicities
Although cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) share many common risk factors, potential molecular mechanisms that may also be shared for these 2 disorders remain unknown.Using an integrative pathway and network analysis, we performed genome-wide association studies in 8155 blacks, 3494 Hispanic American, and 3697 Caucasian American women who participated in the national Women's Health Initiative single-nucleotide polymorphism (SNP) Health Association Resource and the G...
Keywords: Diabetes Mellitus; Gwas; Gene-Gene; Gene-Environment Interaction; Phenotypes; Integrated Approach; Gene-Set Enrichment Analysis
Genome-wide admixture mapping of eGFR and CKD identify European and African ancestry-of-origin loci in U.S. Hispanics/Latinos
Keywords: Ancestry; Admixture; Stratification; Ses; Latino Americans
Related Studies: M5
Genetic variants associated with self-reports of happiness
Related Studies: M5
Association of genetic variation in the tachykinin receptor 3 locus with hot flashes and night sweats in the Women's Health Initiative Study
Objective: Vasomotor symptoms (VMS, ie, hot flashes or night sweats) are reported by many, but not all, women. The extent to which VMS are genetically determined is unknown. We evaluated the relationship of genetic variation and VMS. Methods: In this observational study, we accessed data from three genome-wide association studies (GWAS) (SNP Health Association Resource cohort [SHARe], WHI Memory Study cohort [WHIMSþ], and Genome-Wide Association Studies of Treatment Response in Randomized Clinic...
Keywords: Gene; Gwas; Genome-Wide Association Study; Menopause; Hot Flashes; Vasomotor Symptoms; Night Sweats
Gene by environment investigation of incident lung cancer risk in African-Americans
BACKGROUND: Genome-wide association studies have identified polymorphisms linked to both smoking exposure and risk of lung cancer. The degree to which lung cancer risk is driven by increased smoking, genetics, or gene-environment interactions is not well understood. METHODS: We analyzed associations between 28 single nucleotide polymorphisms (SNPs) previously associated with smoking quantity and lung cancer in 7156 African-American females in the Women's Health Initiative (WHI), then analyzed ma...
Keywords: Smoking; Lung Cancer; Single Nucleotide Polymorphism (Snp); Rs1051730; Lung Cancer Disparities; Gene By Environment Interactions
Related Studies: M5
Genotype imputation in Hispanic-Americans in WHI SHARe
Keywords: Genotype Imputation; Admixed Populations; Quality Score; Concordance Rate; Hispanic-Americans
Related Studies: M5
Trans-ethnic GWAS of pelvic organ prolapse among European American, African American and Hispanic post-menopausal women from the Women’s Health Initiative
Related Studies: M5
Genome-wide association study of coronary artery disease (CAD) in African Americans
Keywords: Coronary Artery Disease; Gwas; Genetic; Genomics
Related Studies: M5
Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25
The genetic contributions to breast cancer development among Latinas are not well understood. Here we carry out a genome-wide association study of breast cancer in Latinas and identify a genome-wide significant risk variant, located 5' of the Estrogen Receptor 1 gene (ESR1; 6q25 region). The minor allele for this variant is strongly protective (rs140068132: odds ratio (OR) 0.60, 95% confidence interval (CI) 0.53-0.67, P=9 × 10(-18)), originates from Indigenous Americans and is uncorrelated with ...
Related Studies: M5
Instrumental variable analysis of alcohol use and cardiometabolic risk in the Women's Health Initiative
Keywords: Mendelian Randomization; Instrumental Analysis; Genome-Wide Association Study; Alcohol; Insulin Resistance; Blood Pressure; Dyslipidemia; Cardiovascular Disease.
Long range and across chromosome admixture-LD: source of confounding in admixture mapping studies
Keywords: Gene; Gwas; Genome-Wide Association Study; Menopause; Hot Flashes; Vasomotor Symptoms
Related Studies: M5
Genome-wide association analysis of incident coronary heart disease (CHD) in African-Americans: A short report
African Americans have the highest rate of mortality due to coronary heart disease (CHD). Although multiple loci have been identified influencing CHD risk in European-Americans using a genome-wide association (GWAS) approach, no GWAS of incident CHD has been reported for African Americans. We performed a GWAS for incident CHD events collected during 19 years of follow-up in 2,905 African Americans from the Atherosclerosis Risk in Communities (ARIC) study. We identified a genome-wide significant ...
Related Studies: M5
Sickle cell trait is not associated with an increased risk of heart failure or abnormalities of cardiac structure and function
Keywords: Stroke; Genetics; Sickle Cell; African American; Cvd
Mixed model association mapping in admixed populations
Keywords: Ancestry; Admixture; Association; Relatedness; Kinship; Latino American
Related Studies: M5
OXTR and DGKH genes, psychological phenotypes, and incident frailty in the Women’s Health Initiative
Keywords: Candidate Genes; Oxytocin Receptor (Oxtr); Diacylglycerol Kinase Eta (Dgkh); Intermediate Variables; Optimism; Pessimism; Subjective Well-Being; Happiness; Cynical Hostility; Aging; Frailty; Coronary Heart Disease; Mortality; Ethnicity
Related Studies: M5
Admixture mapping of pelvic organ prolapse in African Americans from the Women's Health Initiative Hormone Therapy trial
Evidence suggests European American (EA) women have two- to five-fold increased odds of having pelvic organ prolapse (POP) when compared with African American (AA) women. However, the role of genetic ancestry in relation to POP risk is not clear. Here we evaluate the association between genetic ancestry and POP in AA women from the Women's Health Initiative Hormone Therapy trial. Women with grade 1 or higher classification, and grade 2 or higher classification for uterine prolapse, cystocele or ...
Keywords: Pelvic Organ Prolapse; Single Nucleotide Polymorphisms; Admixture Mapping; Post-Menopausal Women; Case-Control Study
Related Studies: M5
Pathway and function-based analysis of genome wide association of body mass index in African Americans
Keywords: Body Mass Index; Genome-Wide Association; African Americans; Pathway; Expression Quantitative Trait Locus
Related Studies: M5
OXTR and DGKH genes, psychological phenotypes, and incident coronary heart disease in the Women’s Health Initiative
Keywords: Candidate Genes; Oxytocin Receptor (Oxtr); Diacylglycerol Kinase Eta (Dgkh); Intermediate Variables; Optimism; Pessimism; Subjective Well-Being; Happiness; Cynical Hostility; Aging; Frailty; Coronary Heart Disease; Mortality; Ethnicity
Related Studies: M5
OXTR and DGKH genes, psychological phenotypes, and mortality in the Women’s Health Initiative
Keywords: Candidate Genes; Oxytocin Receptor (Oxtr); Diacylglycerol Kinase Eta (Dgkh); Intermediate Variables; Optimism; Pessimism; Subjective Well-Being; Happiness; Cynical Hostility; Aging; Frailty; Coronary Heart Disease; Mortality; Ethnicity
Related Studies: M5
Mendelian randomization analysis of white blood count, CVD, cancer, and mortality outcomes in WHI
Related Studies: M5
Broad clinical manifestations of polygenic risk for coronary artery disease in the Women’s Health Initiative
Background: The genetic basis for coronary artery disease (CAD) risk is highly complex. Genome-wide polygenic risk scores (PRS) can help to quantify that risk, but the broader impacts of polygenic risk for CAD are not well characterized. Methods: We measured polygenic risk for CAD using the meta genomic risk score, a previously validated genome-wide PRS, in a subset of genotyped participants from the Women's Health Initiative and applied a phenome-wide association study framework to assess assoc...
Keywords: Polygenic Risk Score; Genetic Risk Score; Phenome-Wide Association Study; Coronary Artery Disease; Cardiovascular Disease; Myocardial Infarction; Coronary Revascularization
A genome-wide association study of breast cancer in women of African ancestry
Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of >1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, which ...
Keywords: None Provided
Related Studies: M5
Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts
The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans.We present results from the largest genome-wide association st...
Keywords: Electrocardiogram; Atrioventricular Conduction; Genome-Wide Association
Stroke prediction in african americans with atrial fibrillation using a genetic risk score
Related Studies: M5
Leveraging population admixture to characterize the heritability of complex traits
Despite recent progress on estimating the heritability explained by genotyped SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense heritability (h(2)) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h(2) due to shared environment or epistasis. We estimate h(2) from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h(2)?). We show that h(2)? = 2FSTC?(1 - ?)h(2),...
Keywords: Genetics; Gwas; Heritability; Cardiovascular; Metabolic
Admixture mapping for blood pressure related phenotype in WHI SHARe individuals
Keywords: Blood Pressure; Hypertension; Admixture; Association; African American; Hispanics
Related Studies: M5
Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology
Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populat...
Estimating kinship in admixed populations.
Genome-wide association studies (GWASs) are commonly used for the mapping of genetic loci that influence complex traits. A problem that is often encountered in both population-based and family-based GWASs is that of identifying cryptic relatedness and population stratification because it is well known that failure to appropriately account for both pedigree and population structure can lead to spurious association. A number of methods have been proposed for identifying relatives in samples from h...
Keywords: Ancestry; Admixture; Association; Relatedness; Kinship; African American; Latino American
Related Studies: M5
A genome-wide interaction analysis of tricyclic/tetracyclic antidepressants and RR and QT intervals: a pharmacogenomics study from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium
BACKGROUND: Increased heart rate and a prolonged QT interval are important risk factors for cardiovascular morbidity and mortality, and can be influenced by the use of various medications, including tricyclic/tetracyclic antidepressants (TCAs). We aim to identify genetic loci that modify the association between TCA use and RR and QT intervals. METHODS AND RESULTS: We conducted race/ethnic-specific genome-wide interaction analyses (with HapMap phase II imputed reference panel imputation) of TCAs ...
Keywords: Pharmacogenomics; Qt Interval; Genetic Epidemiology; Genome-Wide Association Study; Gene-Based Tests
Uncovering loci influencing urinary incontinence in African and Hispanic women: the Women’s Health Initiative SHARe study
Related Studies: M5
Generalizing polygenic risk scores from Europeans to Hispanics/Latinos
Polygenic risk scores (PRSs) are weighted sums of risk allele counts of single-nucleotide polymorphisms (SNPs) associated with a disease or trait. PRSs are typically constructed based on published results from Genome-Wide Association Studies (GWASs), and the majority of which has been performed in large populations of European ancestry (EA) individuals. Although many genotype-trait associations have generalized across populations, the optimal choice of SNPs and weights for PRSs may differ betwee...
Keywords: Genetic Risk Score; Diverse Ancestries; Gwas; Prediction; Validation In An Independent Data Set
Association of sickle cell trait with ischemic stroke among African Americans: a meta-analysis
Importance: African Americans and individuals of African ancestry have a higher risk of stroke compared with non-Hispanic white individuals. Identifying the source of this disparity could provide an opportunity for clinical stroke risk stratification and more targeted therapy. Whether sickle cell trait (SCT) is an indicator of increased risk of ischemic stroke among African Americans is still unclear. Objective: To examine whether SCT is associated with a higher risk of incident ischemic stroke ...
Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations
Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals...
Smoking and genetic risk variation across populations of European, Asian, and African American ancestry - a meta-analysis of chromosome 15q25
Recent meta-analyses of European ancestry subjects show strong evidence for association between smoking quantity and multiple genetic variants on chromosome 15q25. This meta-analysis extends the examination of association between distinct genes in the CHRNA5-CHRNA3-CHRNB4 region and smoking quantity to Asian and African American populations to confirm and refine specific reported associations. Association results for a dichotomized cigarettes smoked per day phenotype in 27 datasets (European anc...
Keywords: None Provided
Related Studies: M5
Meta-analysis of loci associated with age at natural menopause in African-American Women
Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS...
Related Studies: M5
Four susceptibility loci for gallstone disease identified in a meta-analysis of genome-wide association studies
BACKGROUND & AIMS: A genome-wide association study (GWAS) of 280 cases identified the hepatic cholesterol transporter ABCG8 as a locus associated with risk for gallstone disease, but findings have not been reported from any other GWAS of this phenotype. We performed a large-scale, meta-analysis of GWASs of individuals of European ancestry with available prior genotype data, to identify additional genetic risk factors for gallstone disease. METHODS: We obtained per-allele odds ratio (OR) and stan...
Keywords: Gwas; Genetics; Risk Factors; Snp
Related Studies: M5
Multi-ethnic genome-wide association study of decomposed cardioelectric phenotypes illustrates strategies to identify and characterize evidence of shared genetic effects for complex traits
Background: We examined how expanding electrocardiographic trait genome-wide association studies to include ancestrally diverse populations, prioritize more precise phenotypic measures, and evaluate evidence for shared genetic effects enabled the detection and characterization of loci. Methods: We decomposed 10 seconds, 12-lead electrocardiograms from 34 668 multi-ethnic participants (15% Black; 30% Hispanic/Latino) into 6 contiguous, physiologically distinct (P wave, PR segment, QRS interval, S...
Keywords: Electrocardiography; Genetics; Pleiotropy; Multivariate; Ion Channels
Polygenic risk scores and kidney traits in the Hispanic/Latino population: The Hispanic Community Health Study/Study of Latinos
Estimated glomerular filtration rate (eGFR) is used to evaluate kidney function and determine the presence of chronic kidney disease (CKD), a highly prevalent disease in the US1 , 2 , 3 that varies among subgroups of Hispanic/Latino individuals.4 , 5 The polygenic risk score (PRS) is a popular method that uses large genome-wide association studies (GWASs) to provide a strong estimate of disease risk.7 However, due to the limited availability of summary statistics from GWAS meta-analyses based on...
Keywords: Egfr; Prs; Blood Pressure
Related Studies: M5
Kidney stones and the risk of chronic kidney disease among postmenopausal women: Results from The Women's Health Initiative
Keywords: Urinary Tract Stones; Chronic Kidney Disease; End-Stage Kidney Disease (Eskd); Mortality; Hazard Ratio; Postmenopausal Women
Heart failure risk among African American Women with an ICAM1 Missense variant
Background: A common genetic variant of ICAM1 among African-American individuals (rs5491; p.K56M) is associated with heart failure (HF) hospitalization, but whether this risk is specific to heart failure with preserved ejection fraction (HFpEF) remains unclear. Older women are at high risk for HFpEF, and the relationship between rs5491 and HFpEF across the age spectrum is unknown. Objectives: This study assessed risk of HF and its subtypes conferred by ICAM1 p.K56M (rs5491). Methods: Association...
Keywords: Heart Failure; Intercellular Adhesion Molecule-1; Race/Ethnicity; Genetics
Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group
Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conduct...
Keywords: Pharmacogenomics; Qt Interval; Genetic Epidemiology; Genome-Wide Association Study; Gene-Based Tests
Multi-ancestry genome-wide association study of lipid levels incorporating gene-alcohol interactions
An individual's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multi-ancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in Stage 1 (genome-wide discovery) and 66 studies in Stage 2 (focused follow-up), for a total ...
Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium
Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 i...
Keywords: Central Obesity; Hispanic American; Health Disparity; Genetics
Related Studies: M5
Trans-ethnic meta-analysis of white blood cell phenotypes
White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated ...
Keywords: Wbc; Hematology; Genetics; Gwas; Transethnic
Related Studies: M5
SNPs and breast cancer risk prediction for African American and Hispanic women
Keywords: Breast Cancer; Snps; Risk Score; Minorities; Genetics
Related Studies: M5
Model-free estimation of recent genetic relatedness
Genealogical inference from genetic data is essential for a variety of applications in human genetics. In genome-wide and sequencing association studies, for example, accurate inference on both recent genetic relatedness, such as family structure, and more distant genetic relatedness, such as population structure, is necessary for protection against spurious associations. Distinguishing familial relatedness from population structure with genotype data, however, is difficult because both manifest...
Related Studies: M5
Pleiotropic genes for metabolic syndrome and inflammation
Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic ...
Keywords: Pleiotropy; Factor Analysis; Single Nucleotide Polymorphism (Snp); Metabolic Disease; Inflammation
Genome-wide association study of heart rate and its variability in Hispanic/Latino cohorts
BACKGROUND: Although time-domain measures of heart rate variability (HRV) are used to estimate cardiac autonomic tone and disease risk in multi-ethnic populations, the genetic epidemiology of HRV in Hispanics/Latinos has not been characterized. OBJECTIVE: Conduct a genome-wide association study (GWAS) of heart rate (HR) and its variability in the Hispanic Community Health Study / Study of Latinos, Multi-Ethnic Study of Atherosclerosis, and Women's Health Initiative Hispanic SNP-Health Associatio...
Keywords: Autonomic Nervous System; Electrocardiogram (Ecg); Epidemiology; Genetic Association Studies; Ion Channels/Membrane Transport
Replication of loci influencing ages at menarche and menopause in Hispanic women: the Women’s Health Initiative SHARe study
Several genome-wide studies have identified loci associated with reproductive traits, such as ages of menarche and menopause, in women of European ancestry. In this study, we investigated the relevance of these loci in minority US Hispanic women. We utilized data from 3468 women who were genotyped as a part of the Women's Health Initiative SNP Health Association Resource. We replicated associations of eight loci (LRP18, LIN28B, CENPW, INHBA, TMEM38B, ZNF483, NFAT5 and OLFM2) with age at menarche...
Related Studies: M5
A large-scale multi-ancestry genome-wide study accounting for smoking behavior identifies multiple significant loci for blood pressure
Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ~18.8 million SNPs and small insertion/deletion var...
Keywords: Lipids; Blood Pressure; Gene-Environment; Lifestyle; Genetics; Gwas
Genotype imputation of metabochip SNPs using a study-specific reference panel of ~4,000 haplotypes in African Americans from the Women's Health Initiative
Genetic imputation has become standard practice in modern genetic studies. However, several important issues have not been adequately addressed including the utility of study-specific reference, performance in admixed populations, and quality for less common (minor allele frequency [MAF] 0.005-0.05) and rare (MAF < 0.005) variants. These issues only recently became addressable with genome-wide association studies (GWAS) follow-up studies using dense genotyping or sequencing in large samples of n...
Keywords: Genotype Imputation; Metabochip; Internal Reference; African Americans
Genome-wide association study of susceptibility to particulate matter-associated QT prolongation
BACKGROUND: Ambient particulate matter (PM) air pollution exposure has been associated with increases in QT interval duration (QT). However, innate susceptibility to PM-associated QT prolongation has not been characterized. OBJECTIVE: To characterize genetic susceptibility to PM-associated QT prolongation in a multi-racial/ethnic, genome-wide association study (GWAS). METHODS: Using repeated electrocardiograms (1986-2004), longitudinal data on in diameter (), and generalized estimating equations...
Genome-wide association study of platelet count identifies ancestry-specific loci in Hispanic/Latino Americans
Platelets play an essential role in hemostasis and thrombosis. We performed a genome-wide association study of platelet count in 12,491 participants of the Hispanic Community Health Study/Study of Latinos by using a mixed-model method that accounts for admixture and family relationships. We discovered and replicated associations with five genes (ACTN1, ETV7, GABBR1-MOG, MEF2C, and ZBTB9-BAK1). Our strongest association was with Amerindian-specific variant rs117672662 (p value = 1.16 × 10(-28)) i...
Keywords: Novel Blood Cell; Loci; Hispanic
Related Studies: M5
Large multiethnic candidate gene study for C-reactive protein levels: Identification of a novel association at CD36 in African Americans
C-reactive protein (CRP) is a heritable biomarker of systemic inflammation and a predictor of cardiovascular disease (CVD). Large-scale genetic association studies for CRP have largely focused on individuals of European descent. We sought to uncover novel genetic variants for CRP in a multiethnic sample using the ITMAT Broad-CARe (IBC) array, a custom 50,000 SNP gene-centric array having dense coverage of over 2,000 candidate CVD genes. We performed analyses on 7,570 African Americans (AA) from ...
Keywords: None Provided
A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these...
Genetic determinants of pelvic organ prolapse among African American and Hispanic women in the Women’s Health Initiative
Current evidence suggests a multifactorial etiology to pelvic organ prolapse (POP), including genetic predisposition. We conducted a genome-wide association study of POP in African American (AA) and Hispanic (HP) women from the Women's Health Initiative Hormone Therapy study. Cases were defined as any POP (grades 1-3) or moderate/severe POP (grades 2-3), while controls had grade 0 POP. We performed race-specific multiple logistic regression analyses between SNPs imputed to 1000 genomes in relati...
Keywords: None Provided
Related Studies: M5
Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps.
Large-scale whole-genome sequence data sets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole-genome sequence data from the UK10K and 1000 Genomes Project into 35,981 study participants of European ancestry, followed by association analysis with 20 quantitative cardiometabolic and hematological traits. We describe 17 new associations, including 6 rare (minor allele frequency (MAF) < 1%) or low-frequency (1% < MAF < 5...
Keywords: Genetic Factors; Exome Chip; Rare Variants; Inflammation; Inflammatory Biomarkers; Crp
Genome-wide association and population genetic analysis of C-reactive protein in African American and Hispanic American women
C-reactive protein (CRP) is a systemic inflammation marker that predicts future cardiovascular risk. CRP levels are higher in African Americans and Hispanic Americans than in European Americans, but the genetic determinants of CRP in these admixed United States minority populations are largely unknown. We performed genome-wide association studies (GWASs) of 8,280 African American (AA) and 3,548 Hispanic American (HA) postmenopausal women from the Women's Health Initiative SNP Health Association ...
Keywords: C-Reactive Protein; Admixture; Association; African American
Related Studies: M5
Genome-wide characterization of shared and distinct genetic components that influence blood lipid levels in ethnically diverse human populations
Blood lipid concentrations are heritable risk factors associated with atherosclerosis and cardiovascular diseases. Lipid traits exhibit considerable variation among populations of distinct ancestral origin as well as between individuals within a population. We performed association analyses to identify genetic loci influencing lipid concentrations in African American and Hispanic American women in the Women's Health Initiative SNP Health Association Resource. We validated one African-specific hi...
Keywords: Cardiovascular Disease Risk Factors; Admixture; Association; African American
Related Studies: M5
Generalization of adiposity genetic loci to US Hispanic women
Obesity is a public health concern. Yet the identification of adiposity-related genetic variants among United States (US) Hispanics, which is the largest US minority group, remains largely unknown.To interrogate an a priori list of 47 (32 overall body mass and 15 central adiposity) index single-nucleotide polymorphisms (SNPs) previously studied in individuals of European descent among 3494 US Hispanic women in the Women's Health Initiative SNP Health Association Resource (WHI SHARe).Cross-sectio...
Keywords: None Provided
Related Studies: M5
Genome-Wide Association of body fat distribution in African Ancestry populations suggests new loci
Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA...
Keywords: None Provided
Related Studies: M5
Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations
High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA...
Keywords: None Provided
Related Studies: M5
A novel variational Bayes multiple locus Z-statistic for genome-wide association studies with Bayesian model averaging
For many complex traits, including height, the majority of variants identified by genome-wide association studies (GWAS) have small effects, leaving a significant proportion of the heritable variation unexplained. Although many penalized multiple regression methodologies have been proposed to increase the power to detect associations for complex genetic architectures, they generally lack mechanisms for false-positive control and diagnostics for model over-fitting. Our methodology is the first pe...
Keywords: Gwas; Variational Bayes Estimator; Height; Platelet Count; African Americans
Identification, replication, and fine-mapping of loci associated with adult height in individuals of African ancestry
Adult height is a classic polygenic trait of high heritability (h(2) approximately 0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain approximately10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis...
Related Studies: M5
Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption
Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. S...
Keywords: None Provided
Related Studies: M5
Genome-wide association of blood pressure traits by Hispanic/Latino background: the Hispanic Community Health Study/Study of Latinos
Hypertension prevalence varies between ethnic groups, possibly due to differences in genetic, environmental, and cultural determinants. Hispanic/Latino Americans are a diverse and understudied population. We performed a genome-wide association study (GWAS) of blood pressure (BP) traits in 12,278 participants from the Hispanics Community Health Study/Study of Latinos (HCHS/SOL). In the discovery phase we identified eight previously unreported BP loci. In the replication stage, we tested these loc...
Keywords: Diverse Populations; Generalization
Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration
Abstract Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in ...
Genome-wide association study of generalized anxiety symptoms in the Hispanic Community Health Study/Study of Latinos
Although generalized anxiety disorder (GAD) is heritable and aggregates in families, no genomic loci associated with GAD have been reported. We aimed to discover potential loci by conducting a genome-wide analysis of GAD symptoms in a large, population-based sample of Hispanic/Latino adults. Data came from 12,282 participants (aged 18-74) in the Hispanic Community Health Study/Study of Latinos. Using a shortened Spielberger Trait Anxiety measure, we analyzed the following: (i) a GAD symptoms sco...
Keywords: Gwas; Genotype-Environment Interaction; Stressful Life Events; Social Support; Anxiety
Related Studies: M5
Physical activity and the role of common obesity gene variants in FTO with body mass index and obesity in postmenopausal women: The Women’s Health Initiative Study
Alcohol and caffeine intakes may play a role in the development of sudden cardiac death (SCD) because of their effects on cholesterol, blood pressure, heart rate variability, and inflammation.Our objective was to examine the association between long-term alcohol and caffeine intakes and risk of SCD in women.We examined 93,676 postmenopausal women who participated in the Women's Health Initiative Observational Study. Women were enrolled between 1993 and 1998 and were followed until August 2009. W...
Keywords: Fto; Interaction; Obesity; Postmenopausal; Physical Activity
Related Studies: M5
Combined admixture mapping and association analysis identifies a novel blood pressure genetic locus on 5p13: Contributions from the CARe consortium
Admixture mapping based on recently admixed populations is a powerful method to detect disease variants with substantial allele frequency differences in ancestral populations. We performed admixture mapping analysis for systolic blood pressure (SBP) and diastolic blood pressure (DBP), followed by trait-marker association analysis, in 6303 unrelated African-American participants of the Candidate Gene Association Resource (CARe) consortium. We identified five genomic regions (P< 0.001) harboring g...
Keywords: None Provided
Related Studies: M5
Genome-wide association study of body height in African-Americans: the Women’s Health Initiative SNP Health Association Resource (SHARe)
Height is a complex trait under strong genetic influence. To date, numerous genetic loci have been associated with height in individuals of European ancestry. However, few large-scale discovery genome-wide association studies (GWAS) of height in minority populations have been conducted and thus information about population-specific height regulation is limited. We conducted a GWA analysis of height in 8149 African-American (AA) women from the Women's Health Initiative. Genetic variants with P< 5...
Keywords: Body Height; Gwas; Minority; African Americans
Related Studies: M5
Association of sickle cell trait with incidence of coronary heart disease among african american individuals
Importance: The incidence of and mortality from coronary heart disease (CHD) are substantially higher among African American individuals compared with non-Hispanic White individuals, even after adjusting for traditional factors associated with CHD. The unexplained excess risk might be due to genetic factors related to African ancestry that are associated with a higher risk of CHD, such as the heterozygous state for the sickle cell variant or sickle cell trait (SCT). Objective: To evaluate whethe...
A prospective study of soluble receptor for advanced glycation end products and adipokines in association with pancreatic cancer in postmenopausal women
Advanced glycation end products (AGEs) dysregulate adipokines and induce inflammation by binding to their adipocyte receptor (RAGE). Soluble RAGE (sRAGE) prevents AGEs/RAGE signaling. We performed a nested case-control study of the association between sRAGE, adipokines, and incident pancreatic cancer risk in the prospective Women's Health Initiative Study. We individually matched controls (n = 802) to cases (n = 472) on age, race, and blood draw date. We evaluated serum concentrations of sRAGE, ...
Keywords: Biomarker; Ccl2; Body Weight; Composite Biomarker; Pancreatic Cancer; Prospective; Srage
Genome-wide significance thresholds for admixture mapping studies
Abstract Admixture mapping studies have become more common in recent years, due in part to technological advances and growing international efforts to increase the diversity of genetic studies. However, many open questions remain about appropriate implementation of admixture mapping studies, including how best to control for multiple testing, particularly in the presence of population structure. In this study, we develop a theoretical framework to characterize the correlation of local ancestry a...
Keywords: Admixture Mapping; Genome-Wide Association; Multiple Testing; Population Structure; African Americans; Hispanics
Related Studies: M5
DXA versus clinical measures of adiposity as predictors of cardiometabolic diseases and all-cause mortality in postmenopausal women
Objective: To investigate whether dual-energy x-ray absorptiometry (DXA) estimates of adiposity improve risk prediction for cardiometabolic diseases over traditional surrogates, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) in older women. Patients and methods: We analyzed up to 9744 postmenopausal women aged 50 to 79 years participating in the Women's Health Initiative who underwent a DXA scan and were free of cardiovascular disease and diabetes at baseline (Oct...
Keywords: Trunk Fat; Cardiovasular Outcomes; Postmenopausal Women
Genome-wide association of kidney traits in Hispanics/Latinos using dense imputed whole genome sequencing data: The Hispanic Community Health Study/Study of Latinos
Background - Genetic factors that influence kidney traits have been understudied for low frequency and ancestry-specific variants. Methods - This study used imputed whole genome sequencing from the Trans-Omics for Precision Medicine project to identify novel loci for estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR) in up to 12,207 Hispanics/Latinos. Replication was performed in the Women's Health Initiative and the UK Biobank when variants were available. R...
