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Analysis Name and Accession
Name: A Genome-Wide Association Meta-Analysis Of MI In Response To Thiazide Diuretics
Accession: pha003889.1

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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 drug-gene interactions on the outcome of myocardial infarction (MI). The discovery meta-analysis was conducted in 9 studies with GWAS data with European ancestry participants with treated hypertension. Association analysis between genotype and anti-hypertensive medication (thiazide diuretics) with respect to MI was conducted separately within each study cohort according to a pre-specified plan. For each
Analysis Methods
Each study independently implemented a predefined GWAS analysis plan. For the qualitative outcome (MI), multiple sources of information were used to define the event and medication ascertainment. Studies evaluated drug-gene interaction using either (1) Cox proportional hazards regression models with time-varying anti-hypertensive medication exposures, entering at time of treatment and remaining at risk until first MI, death, or last follow-up; or (2) logistic regression in which all hypertensive MI cases were compared to an age- and sex-matched set of population-based hypertensive controls. All regression models included an additive SNP*drug interaction term. Study-specific interaction estimates (β) and standard errors were combined by fixed effects inverse variance weighted meta-analysis using METAL.
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