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Analysis Name and Accession
Name: A Genome-Wide Association Meta-Analysis Of Carotid Artery Plaque
Accession: pha003880.1

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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. Although originally founded by five cohort studies (Age, Gene, Environment, Susceptibility Study - Reykjavik (AGES), Atherosclerosis Risk in Communities (ARIC) study, Cardiovascular Health Study (CHS), Framingham Heart Study, Rotterdam Study, CHARGE has incorporated many genomic and phenotypic data from other cohorts, depending on the phenotype.

Association analysis between genotype and carotid plaque was done 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 dichotomous outcome of carotid plaque, each study used logistic regression models (or general estimating equations clustering on family to account for familial correlations). In primary analyses, all studies were adjusted for age and sex. Some studies made additional adjustments, including adjusting for study site, familial structure or for whether the DNA had been whole-genome amplified or not. For each of the 2.5 million SNPs, each study fit additive genetic models regressing trait on genotype dosage (02 copies of the variant allele). Meta-analysis of regression estimates and standard errors using an inverse-variance weighting approach was conducted using METAL, restricted to autosomal SNPs that were reported in at least two studies and had an average minor allele frequency of at least 1%. For the presence of plaque, a meta-analysis log odds ratio, 95% confidence interval and P value were determined, where the odds ratio represents the increase or decrease in the odds of plaque for each additional copy of the SNP's coded allele.
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