M6 - Population architecture using genomics and epidemiology (PAGE)
Investigator Names and Contact Information
Charles Kooperberg (clk@fredhutch.org)
Introduction/Intent
Specific Aims
Specific Aim #1: To examine the population-based profile of putative genuine variants for a variety of complex diseases and traits, such as cardiovascular diseases (adjudicated myocardial infarction, stroke and cardiovascular death), diabetes, cancer (breast, lung, colorectal), fractures, obesity, and dementia, and to investigate differences by disease subtypes and characteristics.
Specific Aim #2: To evaluate potential modifiers of genetic variant-disease associations, including environmental and life style factors, medication use, as well as three randomized interventions (hormone replacement therapy; low-fat dietary modification; calcium and vitamin D supplementation).
Specific Aim #3: To investigate associations between genuine variants and relevant intermediate outcomes and phenotypic characteristics, such as bone density and body composition, electrocardiogram abnormalities, blood pressure, breast density, leukocyte count, or blood concentrations of lipids, inflammatory markers, insulin, glucose, and hormones.
Results/Findings See the list of over 13 publications on the WHI publications by study lists published WHI papers that have been generated by ancillary studies. A complete list of WHI papers is available in the Papers of this website.
Study Link
Related Papers
Evidence of heterogeneity by race/ethnicity in genetic determinants of QT interval
BACKGROUND: QT interval (QT) prolongation is an established risk factor for ventricular tachyarrhythmia and sudden cardiac death. Previous genome-wide association studies in populations of the European descent have identified multiple genetic loci that influence QT, but few have examined these loci in ethnically diverse populations. METHODS: Here, we examine the direction, magnitude, and precision of effect sizes for 21 previously reported SNPs from 12 QT loci, in populations of European (n = 16...
Keywords: None Provided
Related Studies: M6
Discovery, fine-mapping, and conditional analyses of genetic variants associated with C-reactive protein in multiethnic populations using the Metabochip in the Population Architecture using Genomics and Epidemiology (PAGE) study
C-reactive protein (CRP) is a circulating biomarker indicative of systemic inflammation. We aimed to evaluate genetic associations with CRP levels among non-European-ancestry populations through discovery, fine-mapping and conditional analyses. A total of 30 503 non-European-ancestry participants from 6 studies participating in the Population Architecture using Genomics and Epidemiology study had serum high-sensitivity CRP measurements and ~200 000 single nucleotide polymorphisms (SNPs) genotype...
Keywords: None Provided
Related Studies: M6
Pleiotropy of cancer susceptibility variants on the risk of non-Hodgkin lymphoma: the PAGE Consortium
Risk of non-Hodgkin lymphoma (NHL) is higher among individuals with a family history or a prior diagnosis of other cancers. Genome-wide association studies (GWAS) have suggested that some genetic susceptibility variants are associated with multiple complex traits (pleiotropy).We investigated whether common risk variants identified in cancer GWAS may also increase the risk of developing NHL as the first primary cancer.As part of the Population Architecture using Genomics and Epidemiology (PAGE) c...
Keywords: None Provided
Related Studies: M6
Association of cancer susceptibility variants with risk of multiple primary cancers: The population architecture using genomics and epidemiology study
BACKGROUND: Multiple primary cancers account for approximately 16% of all incident cancers in the United States. Although genome-wide association studies (GWAS) have identified many common genetic variants associated with various cancer sites, no study has examined the association of these genetic variants with risk of multiple primary cancers (MPC). METHODS: As part of the National Human Genome Research Institute (NHGRI) Population Architecture using Genomics and Epidemiology (PAGE) study, we u...
Related Studies: M6
Pleiotropic effects of cancer risk variants on melanoma risk
BACKGROUND: Several regions of the genome show pleiotropic associations with multiple cancers. We sought to evaluate whether 181 single-nucleotide polymorphisms previously associated with various cancers in genome-wide association studies were also associated with melanoma risk. METHODS: We evaluated 2,131 melanoma cases and 20,353 controls from three studies in the Population Architecture using Genomics and Epidemiology (PAGE) study (EAGLE-BioVU, MEC, WHI) and two collaborating studies (HPFS, N...
Keywords: None Provided
Related Studies: M6
The genetic underpinnings of variation in ages at menarche and natural menopause among women from the multi-ethnic population architecture using genomics and epidemiology (PAGE) study: A trans-ethnic meta-analysis
Current knowledge of the genetic architecture of key reproductive events across the female life course is largely based on association studies of European descent women. The relevance of known loci for age at menarche (AAM) and age at natural menopause (ANM) in diverse populations remains unclear. We investigated 32 AAM and 14 ANM previously-identified loci and sought to identify novel loci in a trans-ethnic array-wide study of 196,483 SNPs on the MetaboChip (Illumina, Inc.). A total of 45,364 w...
Keywords: Trans-Ethnic; Menarche; Menopause; Reproductive Timing; Fine-Mapping
Related Studies: M6
Genetic risk factors for BMI and obesity in an ethnically diverse population: results from the population architecture using genomics and epidemiology (PAGE) study
OBJECTIVE: Several genome-wide association studies (GWAS) have demonstrated that common genetic variants contribute to obesity. However, studies of this complex trait have focused on ancestrally European populations, despite the high prevalence of obesity in some minority groups. DESIGN AND METHODS: As part of the ''Population Architecture using Genomics and Epidemiology (PAGE)'' Consortium, we investigated the association between 13 GWAS-identified single-nucleotide polymorphisms (SNPs) and BMI...
Related Studies: M6
Pleiotropic effects of cancer risk variants on prostate cancer risk
Keywords: None Provided
Related Studies: M6
Pleiotropic effects of cancer risk variants on colorectal cancer risk
Keywords: None Provided
Related Studies: M6
Pleiotropic effects of cancer risk variants on lung cancer risk
Keywords: None Provided
Related Studies: M6
Boosting for detection of gene-environment interactions
In genetic association studies, it is typically thought that genetic variants and environmental variables jointly will explain more of the inheritance of a phenotype than either of these two components separately. Traditional methods to identify gene-environment interactions typically consider only one measured environmental variable at a time. However, in practice, multiple environmental factors may each be imprecise surrogates for the underlying physiological process that actually interacts wi...
Keywords: None Provided
Related Studies: M6
New genetic loci link adipocyte and insulin biology to body fat distribution
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI)...
Related Studies: M6
Genetic association of ventricular repolarization and heart rate in the multi-ethnic cohorts of the PAGE Consortium
Keywords: None Provided
Related Studies: M6
Replication of associations between GWAS SNPs and melanoma risk in the Population Architecture Using Genomics and Epidemiology (PAGE) Study
Keywords: None Provided
Related Studies: M6
Generalization and fine mapping of previously identified loci for timing of reproductive traits to multi-ethnic populations: The PAGE Study
Related Studies: M6
Lack of associations of ten candidate coronary heart disease risk genetic variants and subclinical atherosclerosis in four U.S. populations: the Population Architecture using Genomics and Epidemiology (PAGE) Study
A number of genetic variants have been discovered by recent genome-wide association studies for their associations with clinical coronary heart disease (CHD). However, it is unclear whether these variants are also associated with the development of CHD as measured by subclinical atherosclerosis phenotypes, ankle brachial index (ABI), carotid artery intima-media thickness (cIMT) and carotid plaque.Ten CHD risk single nucleotide polymorphisms (SNPs) were genotyped in individuals of European Americ...
Keywords: Subclinical Atherosclerosis; Single Nucleotide Polymorphisms; Minorities
Related Studies: M6
PAGE metabochip project - CHD
Related Studies: M6
Fine-mapping and replication of variants with a reported association to platelet counts in multiple populations using PAGE metabochip results
Related Studies: M6
Fine-mapping and initial characterization of QT interval loci in African Americans
The QT interval (QT) is heritable and its prolongation is a risk factor for ventricular tachyarrhythmias and sudden death. Most genetic studies of QT have examined European ancestral populations; however, the increased genetic diversity in African Americans provides opportunities to narrow association signals and identify population-specific variants. We therefore evaluated 6,670 SNPs spanning eleven previously identified QT loci in 8,644 African American participants from two Population Archite...
Keywords: None Provided
Related Studies: M6
PAGE metabochip project - subclinical atherosclerosis measures
Related Studies: M6
Defining the role of common variation in the genomic and biological architecture of adult human height
Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ~2,000, ~3,700 and ~9,500 SNPs explained ~21%, ~24% and ~29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for gen...
Related Studies: M6
MYH9 polymorphisms and chronic kidney disease progression in CARDIA
Keywords: None Provided
Related Studies: M6
Phenotype-wide association study for exploration of novel SNP and phenotype relationships within PAGE
Keywords: None Provided
Related Studies: M6
Genetic variants associated with obesity and anthropometry: The PAGE study
Keywords: None Provided
Related Studies: M6
Evaluation of the metabochip genotyping array in African Americans and implications for fine mapping of GWAS-identified loci: the PAGE study
The Metabochip is a custom genotyping array designed for replication and fine mapping of metabolic, cardiovascular, and anthropometric trait loci and includes low frequency variation content identified from the 1000 Genomes Project. It has 196,725 SNPs concentrated in 257 genomic regions. We evaluated the Metabochip in 5,863 African Americans; 89% of all SNPs passed rigorous quality control with a call rate of 99.9%. Two examples illustrate the value of fine mapping with the Metabochip in Africa...
Keywords: None Provided
Related Studies: M6
Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations
BACKGROUND/OBJECTIVES: Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (BMI) and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations wi...
Related Studies: M6
FTO obesity risk variant rs8050136 is associated with percentage of energy intake from fat in older adults: The PAGE Study
Keywords: None Provided
Related Studies: M6
PheWAS of metabolic and cancer risk variants with lifestyle factors
Related Studies: M6
The association of anthropometry-related SNPs with age at menarche in the multi-ethnic cohorts of the Population Architecture using Genomics and Epidemiology (PAGE) Consortium
Keywords: None Provided
Related Studies: M6
The influence of obesity status on known lipid variants: Population Architecture using Genomics and Epidemiology (PAGE) study
Related Studies: M6
CHD & metabochip in minorities (working title)
Keywords: Coronary Heart Disease; African Americans; Metabochip; Page Study; Loci
Related Studies: M6
Automatic transformations of the response for genetic association studies, with an application to the Metabochip in the Population Architecture using Genomics and Epidemiology (PAGE) study
Related Studies: M6
Optimizing trans-ethnic tag SNP selection for genome-wide association studies
Related Studies: M6
Design and implementation of the next generation of genome-wide association studies with the multi-ethnic genotyping array
Related Studies: M6
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.
Investigating causal associations between genetically predicted blood metabolite levels and the risks of breast, colorectal, and prostate cancers in African ancestry populations
Related Studies: M6
Generalization and fine mapping of previously identified anthropometric trait loci to multi-ethnic populations and Metabochip-wide analysis: The PAGE Study - part 2
Keywords: Genetics; Ethnicity
Related Studies: M6
Discovery and fine mapping of blood pressure loci to multi-ethnic populations using the MetaboChip array: The PAGE Study
Keywords: Blood Pressure; Genetics; Ethnicity
Related Studies: M6
Fine mapping of previously identified QRS loci to multi-ethnic populations: The PAGE Study
Keywords: Ethicity; Genetics
Related Studies: M6
Fine mapping of previously identified PR loci to multi-ethnic populations: The PAGE Study
Keywords: Ethicity; Genetics
Related Studies: M6
Analysis of familial combined dyslipidemia predisposing factors
Keywords: Genetics
Related Studies: M6
Global fine-mapping of genome-wide association study (GWAS)-identified variants for HDL-C, LDL-C, and triglycerides using the Metabochip in the Population Architecture using Genomics and Epidemiology (PAGE) study
Keywords: Genetics
Related Studies: M6
Global analysis of cross-cancer pleiotropy
Related Studies: M6
Discovery and fine mapping of blood pressure loci to African American and Hispanic individuals using the MetaboChip array: The PAGE Study
Related Studies: M6
Mitochondrial phenome-wide association study using pilot metabochip data
Related Studies: M6
Genetic association of Ankle Brachial Index (ABI) and Lower Extremity Peripheral Artery Disease (PAD) in African American, European, and Hispanic individuals using the MetaboChip array: The PAGE Study
Keywords: None Provided
Related Studies: M6
Evaluating association of blood pressure genetic variants with pulse pressure in multi-ethnic populations: The PAGE Study
Related Studies: M6
Effect of cancer risk variants on multiple primary cancer risk
Related Studies: M6
An investigation of pleiotropy in African Americans in the Population Architecture using Genomics and Epidemiology (PAGE) network
Keywords: None Provided
Related Studies: M6
Prospective associations of coronary heart disease loci in African Americans using the MetaboChip: the PAGE study
Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in African Americans.Up to 8,201 African Americans (including 546 first CHD events) were genotyped using the MetaboChip array in the Ath...
Keywords: Coronary Heart Disease; African Americans; Metabochip; Page Study; Loci
Related Studies: M6
Genetically-driven characterization of detailed morphological electrocardiographic parameters, and their relation to cardiovascular health
Related Studies: M6
Metabolomics of APOL1 carriers with kidney disease
Related Studies: M6
Genetic association of kidney traits in African American, European, Hispanic, and Asian individuals using the MetaboChip array: Discovery and Fine Mapping in the PAGE Consortium
Keywords: None Provided
Related Studies: M6
Evaluating methods for building multi-ethnic polygenic risk-scores
Related Studies: M6
Gene expression analysis of lipid traits in multi-ethnic population
Related Studies: M6
Generalization and fine mapping of previously identified PR loci to multi-ethnic populations: The PAGE Study
Keywords: None Provided
Related Studies: M6
Gene expression analysis of inflammation traits in multi-ethnic population
Related Studies: M6
Gene-acculturation study of obesity among U.S. Hispanics using the MetaboChip array: the PAGE Study
Keywords: None Provided
Related Studies: M6
HNF1B and endometrial cancer risk: Results from the PAGE study
We examined the association between HNF1B variants identified in a recent genome-wide association study and endometrial cancer in two large case-control studies nested in prospective cohorts: the Multiethnic Cohort Study (MEC) and the Women's Health Initiative (WHI) as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. A total of 1,357 incident cases of invasive endometrial cancer and 7,609 controls were included in the analysis (MEC: 426 cases/3,854 controls; WHI:...
Keywords: None Provided
Related Studies: M6
Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia
Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated w...
Keywords: None Provided
Specificity of lipoprotein(a) polygenic risk scores in ancestrally diverse populations
Related Studies: M6
Genetic variants associated with fasting glucose and insulin concentrations in an ethnically diverse population: results from the Population Architecture using Genomics and Epidemiology (PAGE) Study
BACKGROUND: Multiple genome-wide association studies (GWAS) within European populations have implicated common genetic variants associated with insulin and glucose concentrations. In contrast, few studies have been conducted within minority groups, which carry the highest burden of impaired glucose homeostasis and type 2 diabetes in the U.S. METHODS: As part of the 'Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we investigated the association of up to 10 GWAS-identif...
Keywords: None Provided
Related Studies: M6
Genome-wide association study identifying novel variant for fasting insulin and allelic heterogeneity in known glycemic loci in Chilean adolescents: The Santiago Longitudinal Study
Keywords: Adolescent; Glucose; Gwas; Homa-Ir; Insulin
Related Studies: M6
Methylome-wide association study of socioeconomic adversity, type 2 diabetes, and CVD events among 3 large NIH cohorts
Related Studies: M6
Identifying DNA methylation biomarkers that are potentially causally associated with type 2 diabetes and its risk factors among multiethnic populations
Related Studies: M6
A methylome-wide association study of socioeconomic adversity and obesity in the PAGE study
Related Studies: M6
Methylation patterns associated with lifestyle factors (smoking, alcohol, and physical activity) and reproductive traits in PAGE multi-ethnic populations
Related Studies: M6
Role of single nucleotide polymorphisms in the association between apolipoprotein L1 renal risk variants and renal outcomes
Related Studies: M6
Analyses of biomarker traits in diverse UK biobank participants identify associations missed by european-centric analysis strategies
Related Studies: M6
Redefining replication in multi-ancestry genome-wide association studies
Related Studies: M6
Application of novel hematological trait genetic risk scores in multi-ethnic populations
Related Studies: M6
Transcriptome-wide association study of blood cell traits in African American and Hispanic/Latino Populations
Related Studies: M6
Trans-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
Related Studies: M6
Comparing trans-ethnic meta-analysis methods using the PAGE Study
Related Studies: M6
Identifying protein biomarkers that are associated with type 2 diabetes and its risk factors using genetic instruments among multiethnic populations
Related Studies: M6
The influence of sodium and potassium in the context of genetic variants associated with blood pressure in the Population Architecture using Genomics and Epidemiology (PAGE) study
Related Studies: M6
Associations of combined genetic and lifestyle risks with incident diabetes in the Women’s Health Initiative
Related Studies: M6
Association of mendelian proteinuric kidney disease genes with kidney disease markers in ancestrally diverse populations
Related Studies: M6
Evaluation, characterization and improvement of trans-ancestral polygenic risk scores for lipid traits
Related Studies: M6
Evaluation of multiethnic PRS for obesity
Related Studies: M6
Methylation patterns associated with CRP and IL-6 inflammation traits in racially and ethnically diverse populations
Related Studies: M6
Predicted gene expression in ancestrally diverse populations leads to discovery of novel susceptibility loci for lifestyle and cardiometabolic traits
Related Studies: M6
A large-scale multi-ethnic genome-wide association study of coronary artery disease
Related Studies: M6
Importance of genetic studies of cardiometabolic disease in under-represented populations
Keywords: Race And Ethnicity; Genetic; Association Studies; Epidemiology; Cardiovascular Disease; Genetics
Related Studies: M6
MEGA analysis of age at menarche, age at natural menopause and other female reproductive traits
Related Studies: M6
Genetic studies of body mass index yield new insights for obesity biology
Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have signific...
Keywords: Giant Consortium; Obesity; Genetics
Related Studies: M6
Signals of selection and population differentiation in metabolic trait-related genes
Keywords: Population Genetics; Metabochip; Fst; African Americans
Related Studies: M6
The influence of obesity-related single nucleotide polymorphisms on BMI across the life course: the PAGE study
Evidence is limited as to whether heritable risk of obesity varies throughout adulthood. Among >34,000 European Americans, aged 18-100 years, from multiple U.S. studies in the Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we examined evidence for heterogeneity in the associations of five established obesity risk variants (near FTO, GNPDA2, MTCH2, TMEM18, and NEGR1) with BMI across four distinct epochs of adulthood: 1) young adulthood (ages 18-25 years), adulthood (ag...
Keywords: None Provided
Related Studies: M6
Genetic underpinnings of the heterogenous impact of obesity on lipid levels and cardiovascular disease
Related Studies: M6
Estimating heritability explained by local ancestry and evaluating stratification bias in admixture mapping from summary statistics
Related Studies: M6
Evaluation, characterization and improvement of trans-ancestral polygenic risk scores for blood pressure traits
Related Studies: M6
Associations of smoking and somatic DNA mutations in colorectal cancer: results from an international tumor sequencing consortium
Related Studies: M6
Genetic discovery and risk characterization in Type 2 Diabetes across diverse populations
Genomic discovery and characterization of risk loci for type 2 diabetes (T2D) have been conducted primarily in individuals of European ancestry. We conducted a multiethnic genome-wide association study of T2D among 53,102 cases and 193,679 control subjects from African, Hispanic, Asian, Native Hawaiian, and European population groups in the Population Architecture Genomics and Epidemiology (PAGE) and Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortia. In individuals of African a...
Related Studies: M6
A saturated map of common genetic variants associated with human height 1 from 5.4 Million individuals of diverse ancestries
Related Studies: M6
Type 2 diabetes polygenic risk score interactions with lifestyle risk factors in Black Americans
Related Studies: M6
Multi-ancestral analysis of inflammation-related genetic variants and C-reactive protein in the Population Architecture using Genomics and Epidemiology Study
C-reactive protein (CRP) is a biomarker of inflammation. Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with CRP concentrations and inflammation-related traits such as cardiovascular disease, type 2 diabetes mellitus, and obesity. We aimed to replicate previous CRP-SNP associations, assess whether these associations generalize to additional race/ethnicity groups, and evaluate inflammation-related SNPs for a potentially pleiotropic associa...
Keywords: None Provided
Related Studies: M6
The next PAGE in understanding complex traits: Design for the analysis of population architecture using genetics and epidemiology (PAGE) study
Genetic studies have identified thousands of variants associated with complex traits. However, most association studies are limited to populations of European descent and a single phenotype. The Population Architecture using Genomics and Epidemiology (PAGE) Study was initiated in 2008 by the National Human Genome Research Institute to investigate the epidemiologic architecture of well-replicated genetic variants associated with complex diseases in several large, ethnically diverse population-bas...
Keywords: None Provided
Related Studies: M6
Associations between incident ischemic stroke events and stroke and cardiovascular disease-related GWAS SNPs in the Population Architecture Using Genomics and Epidemiology (PAGE) Study
Genome-wide association studies (GWAS) have identified loci associated with ischemic stroke (IS) and cardiovascular disease (CVD) in European-descent individuals, but their replication in different populations has been largely unexplored.Nine single nucleotide polymorphisms (SNPs) selected from GWAS and meta-analyses of stroke, and 86 SNPs previously associated with myocardial infarction and CVD risk factors, including blood lipids (high density lipoprotein [HDL], low density lipoprotein [LDL], ...
Keywords: None Provided
Related Studies: M6
Association of genetic variants and incident coronary heart disease in multiethnic cohorts: The PAGE Study
Genome-wide association studies identified several single nucleotide polymorphisms (SNP) associated with prevalent coronary heart disease (CHD), but less is known of associations with incident CHD. The association of 13 published CHD SNPs was examined in 5 ancestry groups of 4 large US prospective cohorts.The analyses included incident coronary events over an average 9.1 to 15.7 follow-up person-years in up to 26 617 white individuals (6626 events), 8018 black individuals (914 events), 1903 Hisp...
Keywords: Incident Coronary Heart Disease; Single Nucleotide Polymorphisms; Minorities
Related Studies: M6
Generalization and attenuation of association results from European GWAS in populations of non-European ancestry
The vast majority of genome-wide association study (GWAS) findings reported to date are from populations with European Ancestry (EA), and it is not yet clear how broadly the genetic associations described will generalize to populations of diverse ancestry. The Population Architecture Using Genomics and Epidemiology (PAGE) study is a consortium of multi-ancestry, population-based studies formed with the objective of refining our understanding of the genetic architecture of common traits emerging ...
Keywords: None Provided
Related Studies: M6
Consistent directions of effect for established type 2 diabetes risk variants across populations: The Population Architecture using Genomics and Epidemiology (PAGE) Consortium
Common genetic risk variants for type 2 diabetes (T2D) have primarily been identified in populations of European and Asian ancestry. We tested whether the direction of association with 20 T2D risk variants generalizes across six major racial/ethnic groups in the U.S. as part of the Population Architecture using Genomics and Epidemiology Consortium (16,235 diabetes case and 46,122 control subjects of European American, African American, Hispanic, East Asian, American Indian, and Native Hawaiian a...
Keywords: None Provided
Related Studies: M6
Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci
Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Ameri...
Related Studies: M6
Discovery and fine mapping of genetic loci associated with blood pressure traits in Hispanics and African Americans
Despite the substantial burden of hypertension in US minority populations, few genetic studies of blood pressure have been conducted in Hispanics and African Americans, and it is unclear whether many of the established loci identified in European-descent populations contribute to blood pressure variation in non-European descent populations. Using the Metabochip array, we sought to characterize the genetic architecture of previously identified blood pressure loci, and identify novel cardiometabol...
Keywords: Genetics; Blood Pressure; Hispanics; African Americans; Metabochip; Hypertension
Related Studies: M6
Generalization and fine mapping of red blood cell trait genetic associations to multi-ethnic populations: The PAGE Study
Red blood cell (RBC) traits provide insight into a wide range of physiological states and exhibit moderate to high heritability, making them excellent candidates for genetic studies to inform underlying biologic mechanisms. Previous RBC trait genome-wide association studies were performed primarily in European- or Asian-ancestry populations, missing opportunities to inform understanding of RBC genetic architecture in diverse populations and reduce intervals surrounding putative functional SNPs t...
Related Studies: M6
Type 2 diabetes polygenic risk score demonstrates context-dependent effects and associations with type 2 diabetes-related risk factors and complications across diverse populations
Related Studies: M6
Analysis of metabolic syndrome components in >15 000 african americans identifies pleiotropic variants: results from the population architecture using genomics and epidemiology study
Metabolic syndrome (MetS) refers to the clustering of cardiometabolic risk factors, including dyslipidemia, central adiposity, hypertension, and hyperglycemia, in individuals. Identification of pleiotropic genetic factors associated with MetS traits may shed light on key pathways or mediators underlying MetS.Using the Metabochip array in 15 148 African Americans from the Population Architecture using Genomics and Epidemiology (PAGE) study, we identify susceptibility loci and investigate pleiotro...
Keywords: Metabolic Syndrome; Genetics; Meta-Analysis; Asset
Related Studies: M6
Genetic determinants of lipid traits in diverse populations from the Population Architecture using Genomics and Epidemiology (PAGE) Study
For the past five years, genome-wide association studies (GWAS) have identified hundreds of common variants associated with human diseases and traits, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. Approximately 95 loci associated with lipid levels have been identified primarily among populations of European ancestry. The Population Architecture using Genomics and Epidemiology (PAGE) study was established in 2008...
Keywords: None Provided
Related Studies: M6
A systematic mapping approach of 16q12.2/FTO and BMI in more than 20,000 African Americans narrows in on the underlying functional variation: results from the Population Architecture using Genomics and Epidemiology (PAGE) study
Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-m...
Keywords: None Provided
Related Studies: M6
Phenome-wide association study (PheWAS) for detection of pleiotropy within the Population Architecture Using Genomics and Epidemiology (PAGE) Network
Using a phenome-wide association study (PheWAS) approach, we comprehensively tested genetic variants for association with phenotypes available for 70,061 study participants in the Population Architecture using Genomics and Epidemiology (PAGE) network. Our aim was to better characterize the genetic architecture of complex traits and identify novel pleiotropic relationships. This PheWAS drew on five population-based studies representing four major racial/ethnic groups (European Americans (EA), Afr...
Related Studies: M6
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
Fine-mapping of QT regions in global populations refines previously identified QT loci and identifies signals unique to African and Hispanic descent populations
BACKGROUND: The electrocardiographically measured QT interval (QT) is heritable and its prolongation is an established risk factor for several cardiovascular DISEASES: Yet, most QT genetic studies have been performed in European ancestral populations, possibly reducing their global relevance. OBJECTIVE: To leverage diversity and improve biologic insight, we fine-mapped 16 of the 35 previously identified QT loci (46%) in populations of African American (n=12,410) and Hispanic/Latino (n=14,837) an...
Keywords: None Provided
Related Studies: M6
Effects of smoking on the genetic risk of obesity: the population architecture using genomics and epidemiology study
Although smoking behavior is known to affect body mass index (BMI), the potential for smoking to influence genetic associations with BMI is largely unexplored.As part of the 'Population Architecture using Genomics and Epidemiology (PAGE)' Consortium, we investigated interaction between genetic risk factors associated with BMI and smoking for 10 single nucleotide polymorphisms (SNPs) previously identified in genome-wide association studies. We included 6 studies with a total of 56,466 subjects (1...
Keywords: Obesity; Body Mass Index; Genome-Wide Association Study; Genetic Risk Factor; Smoking Interactions; Genetic Epidemiology
Related Studies: M6
Fine mapping and identification of BMI loci in African Americans
Genome-wide association studies (GWASs) primarily performed in European-ancestry (EA) populations have identified numerous loci associated with body mass index (BMI). However, it is still unclear whether these GWAS loci can be generalized to other ethnic groups, such as African Americans (AAs). Furthermore, the putative functional variant or variants in these loci mostly remain under investigation. The overall lower linkage disequilibrium in AA compared to EA populations provides the opportunity...
Keywords: None Provided
Related Studies: M6
Post-Genome-Wide Association Study challenges for lipid traits: describing age as a modifier of gene-lipid associations in the Population Architecture Using Genomics and Epidemiology (PAGE) Study
Numerous common genetic variants that influence plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride distributions have been identified via genome-wide association studies (GWAS). However, whether or not these associations are age-dependent has largely been overlooked. We conducted an association study and meta-analysis in more than 22,000 European Americans between 49 previously identified GWAS variants and the three lipid traits, stratified...
Keywords: None Provided
Related Studies: M6
Investigation of gene-by-sex interactions for lipid traits in diverse populations from the population architecture using genomics and epidemiology study
BACKGROUND: High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels are influenced by both genes and the environment. Genome-wide association studies (GWAS) have identified ~100 common genetic variants associated with HDL-C, LDL-C, and/or TG levels, mostly in populations of European descent, but little is known about the modifiers of these associations. Here, we investigated whether GWAS-identified SNPs for lipid traits exhibited he...
Keywords: Lipids; Genetics; Cardiovascular Disease; Heterogeneity; Sex-Specific Effect; Association Study
Related Studies: M6
Transethnic insight into the genetics of glycaemic traits: fine-mapping results from the Population Architecture using Genomics and Epidemiology (PAGE) consortium
AIMS/HYPOTHESIS: Elevated levels of fasting glucose and fasting insulin in non-diabetic individuals are markers of dysregulation of glucose metabolism and are strong risk factors for type 2 diabetes. Genome-wide association studies have discovered over 50 SNPs associated with these traits. Most of these loci were discovered in European populations and have not been tested in a well-powered multi-ethnic study. We hypothesised that a large, ancestrally diverse, fine-mapping genetic study of glycae...
Keywords: Ethicity; Genetics
Related Studies: M6
No evidence of interaction between known lipid-associated genetic variants and smoking in the multi-ethnic PAGE population
Genome-wide association studies (GWAS) have identified many variants that influence high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and/or triglycerides. However, environmental modifiers, such as smoking, of these known genotype-phenotype associations are just recently emerging in the literature. We have tested for interactions between smoking and 49 GWAS-identified variants in over 41,000 racially/ethnically diverse samples with lipid levels from the Population Archit...
Related Studies: M6
Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained
Genome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individua...
Keywords: None Provided
Related Studies: M6
Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia
Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated with other cancers may be additionally associated with endometrial cancer. We examined 213 SNPs previously associated with 14 other cancers for their associations with endometrial ca...
Keywords: None Provided
Related Studies: M6
Replication of genetic loci for ages at menarche and menopause in the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) study
STUDY QUESTION: Do genetic associations identified in genome-wide association studies (GWAS) of age at menarche (AM) and age at natural menopause (ANM) replicate in women of diverse race/ancestry from the Population Architecture using Genomics and Epidemiology (PAGE) Study? SUMMARY ANSWER: We replicated GWAS reproductive trait single nucleotide polymorphisms (SNPs) in our European descent population and found that many SNPs were also associated with AM and ANM in populations of diverse ancestry....
Keywords: None Provided
Related Studies: M6
Genetic pleiotropy underpinning obesity and inflammation in self-identified Hispanic/Latino populations
Related Studies: M6
Probing the diabetes and colorectal cancer relationship using gene – environment interaction analyses
Related Studies: M6
A step-by-step guide how to treat race or ethnicity and genetic ancestry in genomic studies of diverse populations
Related Studies: M6
Multi-ethnic GWAS and fine-mapping of glycemic traits identify novel loci in the PAGE Study
Aims/hypothesis: Type 2 diabetes is a growing global public health challenge. Investigating quantitative traits, including fasting glucose, fasting insulin and HbA1c, that serve as early markers of type 2 diabetes progression may lead to a deeper understanding of the genetic aetiology of type 2 diabetes development. Previous genome-wide association studies (GWAS) have identified over 500 loci associated with type 2 diabetes, glycaemic traits and insulin-related traits. However, most of these fin...
Keywords: Fine-Mapping; Genome-Wide Association Study; Glucose; Glycaemic Traits; Hba1c; Insulin; Transethnic Population
Genetic variation in DEFB1 modifies penetrance of APOL1 high-risk genotypes for kidney disease
Related Studies: M6
Genetic variation and reproductive timing: African American women from the Population Architecture Using Genomics and Epidemiology (PAGE) Study
Age at menarche (AM) and age at natural menopause (ANM) define the boundaries of the reproductive lifespan in women. Their timing is associated with various diseases, including cancer and cardiovascular disease. Genome-wide association studies have identified several genetic variants associated with either AM or ANM in populations of largely European or Asian descent women. The extent to which these associations generalize to diverse populations remains unknown. Therefore, we sought to replicate...
Keywords: None Provided
Related Studies: M6
Causal effects on complex traits are similar across segments of different continental ancestries within admixed individuals
Related Studies: M6
Assortative mating patterns across contemporary human populations
Related Studies: M6
Impact of trans-ancestry meta-analysis on the performance of genetic scores for multiple adiposity-related traits
Related Studies: M6
Interactions with type 2 diabetes genetic risk factors among African Americans
Related Studies: M6
The use of TRACTOR to improve PRS in admixed populations
Related Studies: M6
Pleiotropic associations of risk variants identified for other cancers with lung cancer risk: The PAGE and TRICL consortia
Genome-wide association studies have identified hundreds of genetic variants associated with specific cancers. A few of these risk regions have been associated with more than one cancer site; however, a systematic evaluation of the associations between risk variants for other cancers and lung cancer risk has yet to be performed.We included 18023 patients with lung cancer and 60543 control subjects from two consortia, Population Architecture using Genomics and Epidemiology (PAGE) and Transdiscipl...
Related Studies: M6
Genome-wide association analyses of Hispanic/Latino populations to map and characterize disease loci for coronary heart disease, stroke and hypertension
Related Studies: M6
The additive and multiplicative interactions between hormone therapy use and polygenetic risk scores for multiple health outcomes
Keywords: Interaction; Hormone Therapy; Polygenic Risk Scores; Prs; Additive; Multiplicative
Related Studies: M6
Epigenome-wide association study meta-analysis of BMI in African Americans
Related Studies: M6
Variation in associations between genetic risk scores and cardiometabolic phenotypes across PAGE biobanks and cohort studies
Related Studies: M6
Leveraging diversity within PAGE to improve the predictive performance of PGS
Related Studies: M6
Efficient lasso framework for admixture-aware polygenic risk scores
Related Studies: M6
Improving polygenic risk prediction in admixed populations by explicitly modeling ancestral-specific effects via GAUDI
Polygenic risk scores (PRS) have shown successes in clinics, but most PRS methods focus only on participants with distinct primary continental ancestry without accommodating recently-admixed individuals with mosaic continental ancestry backgrounds for different segments of their genomes. Here, we develop GAUDI, a novel penalized-regression-based method specifically designed for admixed individuals. GAUDI explicitly models ancestry-differential effects while borrowing information across segments ...
Related Studies: M6
Improving polygenic prediction for depression for clinical use
Related Studies: M6
Epidemiology Estimates of Alpha-1 Antitrypsin Deficiency (AATD) in the United States
Related Studies: M6
Development of an ancestry-informed ADRD polygenic risk model in African American and Latíno populations
Keywords: Ancestry; Polygenic Risk Model; African American; Latíno; Alzheimer'S
Related Studies: M6
