The ARIC (Atherosclerosis Risk in Communities) study is a population-based prospective cohort study of cardiovascular disease and its risk factors 
. ARIC includes 15,792 persons aged 45–64 years at baseline (1987–89), randomly chosen from four US communities. Of these individuals, 4,266 are self-reported African Americans. Cohort members completed four clinic examinations, conducted approximately three years apart between 1987 and 1998, and followed with annual phone interviews since 1987.
Incident CHD in ARIC was ascertained by contacting participants annually, identifying hospitalizations and deaths during the prior year, and by surveying discharge lists from local hospitals and death certificates from state vital statistics offices for potential cardiovascular events 
. A CHD event was defined as a validated definite or probable hospitalized MI, a definite CHD death, an unrecognized MI defined by ARIC ECG readings, or coronary revascularization. Participants were excluded from analyses if they had a positive or unknown history of prevalent stroke, transient ischemic attack/stroke symptoms, or CHD at the initial visit and/or being of non–African American ethnicity. Real-time, B-mode ultrasound was used to evaluate the carotid arterial intima-media wall thickness as an indicator of atherosclerosis in the ARIC study and the detailed description of its measurement is described elsewhere 
Genotyping was done in 15,020 ARIC participants using the Affymetrix Genome-Wide Human SNP Array 6.0. A total of 3,182 individuals remained after excluding individuals of non African American ethnicity, subjects who did not consent DNA use, unintentional duplicates with higher missing genotype rates, suspected mixed/contaminated samples, scans from one problem plate, samples with a mismatch between called and phenotypic sex, samples with genotype mismatch with 39 previously genotyped SNPs, suspected first-degree relative of an included individual, and genetic outliers based on average IBS statistics and principal components analysis using EIGENSTRAT. SNPs were excluded due to having no chromosome location, being monomorphic, having a call rate <95% and HWE-p<10−5. In this analysis, we considered only variants with a MAF greater than 10%.
Cox proportional hazards models with adjustment for age, gender and the first three principal components derived from EIGENSTRAT were used to estimate CHD hazard rate ratios (HRs) over a 19-year period (362 cases) under an additive genetic model. These analyses were done using PLINK and an R application for survival regression analyses. We define as “genome-wide significant” all associations with p<5×10−8. We define replication to be a significant (p<0.05) and directionally consistent association in an independent sample.
The WHI has two major components: (1) a clinical trial that enrolled and randomized 68,132 women ages 50–79 into at least one of three clinical trials; and (2) an observational study that enrolled 93,676 women ages 50–79 into a parallel prospective cohort study 
. WHI participants were recruited from 1993–1998 at 40 clinical centers across the U.S. During follow-up, incident CHD events were adjudicated locally and centrally from medical records including hospital discharge summaries, ICD-9 codes, diagnostic, laboratory, surgical, and pathology reports by trained physicians blinded to randomized intervention and exposure status 
. In the WHI replication sample, CHD was defined as MI, coronary revascularization, hospitalized angina, or CHD death. Definite and probable nonfatal MI required overnight hospitalization and was defined according to an algorithm based on standardized criteria using cardiac pain, cardiac enzymes and troponin levels, and ECG findings. CHD death was defined as death consistent with underlying cause of CHD plus one or more of the following: hospitalization for MI within 28 days prior to death, previous angina or myocardial infarction, death due to a procedure related to CHD, or a death certificate consistent with underlying cause of atherosclerotic CHD.
Of a total of 26,045 (17%) women from minority groups, 8,515 self identified African American women who had consented to genetic research were eligible for the WHI GWAS project. Genotyping was performed on the Affymetrix 6.0 array. After excluding samples due to genotyping failure, cryptic relatedness, and discrepancy between genetic ancestry and self-reported race, there were 8,421 WHI African Americans. Participants were further excluded from analyses if they had a positive or unknown history of prevalent stroke, transient ischemic attack/stroke symptoms, or CHD at the initial visit. A total of 862 incident first CHD events occurred among 8,155 eligible African American women without baseline CHD (). The mean age at study entry was 61.6+/−7.0 years (range 50–79). The mean baseline age of the cases was 64.2+/−7.2, and the mean baseline age of the non-cases was 61.3+/−6.9. The mean time to CHD event was 5.29+/−3.19 years. The mean age at CHD event was 69.5+/−7.5 years.
Baseline characteristics of the WHI sample.
This study was approved by the participating institutional IRBs, and all ARIC and WHI participants provided written informed consent, involving the sharing of data with the scientific community.
The Pathobiolobical Determinants of Atherosclerosis in Youth (PDAY) study is composed of subjects who were 15 to 34 years of age when they died of non-CVD related causes (accidents, homicides or suicides). The purpose of PDAY was to evaluate early development of atherosclerosis 
. For this replication analysis, we genotyped rs1859023 in 2,794 individuals from PDAY - 1,452 African Americans and 1,342 European Americans and tested the association with fatty streak area in the right coronary artery.