Rationale, design, and methodology of the Women's Genome Health Study: a genome-wide association study of more than 25,000 initially healthy american women.

The primary aim of the Women's Genome Health Study (WGHS) is to create a comprehensive, fully searchable genome-wide database of >360 000 single nucleotide polymorphisms among at least 25 000 initially healthy American women participating in the ongoing NIH-funded Women's Health Study (WHS). These women have already been followed over a 12-year period for major incident health events including but not limited to myocardial infarction, stroke, cancer, diabetes, osteoporosis, venous-thromboembolism, cognitive decline, and common visual disorders such as age- related macular degeneration and cataracts. Investigations within the WGHS will seek to identify relevant patterns of genetic polymorphism that predict future disease states in otherwise healthy American women, and to evaluate patterns of genetic polymorphism that relate to multiple intermediate phenotypes including blood-based determinants of disease that were measured at baseline for each study participant. By linking genome-wide data to the existing epidemiologic databank of the parent WHS, which includes comprehensive dietary, behavioral, and traditional exposure data on each participant since cohort inception in 1992, the WGHS will also allow exploration of gene-environment and gene-gene interactions as they relate to incident disease states. Thus, with continued follow-up of the WHS, the WGHS provides a unique scientific resource-a full-cohort, prospective, genome-wide association study among initially healthy American women.