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Chunk #21 — METHODS — Polygenic scoring.

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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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Prediction accuracy comes from a two-step process where we first regress the phenotype on a standard set of covariates without including the PRS. Then, the PRS predictor is added and the difference in the coefficient of determination (R2) is calculated. For our quantitative phenotypes, AgeSmk, CigDay, and DrnkWk, the predictive power of the PRS is the change in the R2 in going from the regression without the PRS to the regression with the PRS. For our two binary phenotypes, SmkInit and SmkCes, we measure the incremental pseudo-R2 from probit regressions. 95% confidence intervals around all R2 values are bootstrapped with 1000 repetitions each. The same polygenic scoring procedure was applied to the MTAG results (Supplementary Table 32).