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Analysis Name and Accession
Name: A Genome-Wide Association Meta-Analysis For Incident Coronary Heart Disease
Accession: pha003910.1

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Analysis Description
The Cohorts for Heart and Aging Research in Genomic Epimiology (CHARGE) consortium was formed to facilitate genome-wide association study meta-analyses and replication among large, well-phenotyped cohort studies. CHARGE has incorporated many genomic and phenotypic data from other cohorts, depending on the phenotype. The basic design was estimation of SNP effects on the outcome of incident CHD in the five prospective cohort studies of European ancestry. The discovery meta-analysis was conducted in 24,024 subjects with 2406 incident CHD cases with GWAS data. Association analysis between genotype and CHD was conducted separately within each study according to a pre-specified plan. For each SNP, GWAS-specific results were combined using inverse-variance weighted meta-analysis in METAL.
Analysis Methods
Each study independently implemented a predefined GWAS analysis plan. Each contributing cohort had its own GWAS platform, variant calling algorithm, call rate filter, HWE filter, MAF filter and analytic software. For incident CHD, association with SNP genotypes used a 1 df additive model adjusted for covariates (age, sex and study-specific). Analytic methods varied by study (AGES: Cox regression, excluding subjects with prevalent events; ARIC: Cox regression, entry at baseline, censoring at death or loss to follow-up; CHS: Cox regression, entry at blood draw (baseline), censoring at death or loss to follow-up; FHS: Cox regression with clustering on families, entry at time of blood draw, censoring at death or loss to follow-up; RS: Cox regression, entry at baseline, censoring at death or loss to follow-up). Study-specific hazard ratios (HR) and standard errors were determined by R (AGES, CHS), ProbABEL (ARIC, RS) and coxph in R (FHS). Meta-analysis was conducted by fixed effects inverse variance weighted meta-analysis using METAL.
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