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Chunk #13 — Method — Candidate Genes

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Rare nonsynonymous exonic variants in addiction and behavioral disinhibition.
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yes

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In addition to evaluating all SNPs on the integrated array, we also evaluated 172 candidate addiction genes from two published sources(30, 31), and a shorter list of “high priority” genes implicated in smoking and drinking from GWAS meta-analyses of tobacco and alcohol use(22, 24, 25, 32). Of the 172 genes, 151 contained polymorphic nonsynonymous variants in our sample. We report burden test results on the full 151, and also report single variant tests of nonsynonymous variants in the shorter list of high priority genes (i.e., CHRNA5, CHRNA3, CHRNA6, CHRNB4, CYP2A6, CYP2B6, ELGN2, DBH, ALDH2, ADH1B, and AUTS2). The meta-analyses evaluated smoking and alcohol consumption, measures readily available in large epidemiological samples, and we restricted our tests to similar phenotypes in the present study. Specifically, we tested these 11 genes on nicotine (exposed), alcohol dependence (full sample and exposed individuals), and drinking (full sample and exposed individuals).