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Chunk #10 — Materials and methods — Data Analysis — Genome-wide association and meta-analyses

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Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood.
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Genome-wide association testing was performed using PROBABEL (Aulchenko, Struchalin & van Duijn, 2010), GWAS software for use with probabilistically imputed genotype dosages. Tests were specified as linear regressions of additive SNP effects, controlling for the top five ancestral PCA dimensions as covariates. Meta-analysis procedures proposed by deBakker and colleagues (de Bakker et al., 2008) were used to aggregate results across the three studies. Specifically, aggregate beta coefficients and associated standard errors were computed as follows: β=∑i[βi/(SEi)2]∑i[1/(SEi)2] SE=1∑i[1/(SEi)2] where i indexes study number. Given the use of a common genotyping platform (Illumina Human660W-Quad v1 DNA Analysis BeadChips) and genotyping lab (Mayo Clinic), many common pitfalls in GWAS meta-analysis were avoided, including strand orientation mismatches, imputation reference sample heterogeneity, variable QC criteria, etc.