- Analysis Name and Accession
Analysis Name: A Genome-Wide Association Meta-Analysis Of CVD In Response To ACE Inhibitors
Analysis Accession: pha003890.1
- 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 cardiovascular disease (CVD). 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 (ACE inhibitor) with respect to CVD was conducted separately within each study cohort 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. For the qualitative outcome (CVD), 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 CVD event, death, or last follow-up; or (2) logistic regression in which all hypertensive CVD 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.
- Analysis Plots
The following plots were generated by dbGaP based on the data that was submitted and are not
necessarily from any publications noted under Selected Publications.
- Selected Publications