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Chunk #2 — METHODS — Generation of summary statistics.

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Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.
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GWAS summary statistics were generated in each study sample using RVTESTS53 according to a standard analysis plan. Studies composed primarily of classically related individuals (e.g., family studies) first regressed out covariates including genetic principal components under a linear model, inverse-normalized the residuals (except for 23andMe), and tested for an additive effect of each variant under a linear mixed model with a genetic kinship matrix. Family studies followed this analysis for all phenotypes, even binary phenotypes such as smoking initiation and cessation. Studies of entirely classically unrelated individuals followed the same analysis for quasi-continuous phenotypes (AgeSmk, CigDay, DrnkWk), but estimated additive genetic effects under a logistic model for binary phenotypes (SmkInit and SmkCes).