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:

1. Enhance the statistical power for research specific to groups defined by race and ethnicity
2. Discover (or replicate) genes associated with quantitative traits (such as blood pressure, blood lipids) in these groups
3. 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.
4. 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.

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.

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