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Chunk #15 — Results — Genomewide association study of nicotine withdrawal symptoms: rs31746 associated with NicW across populations

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A protocadherin gene cluster regulatory variant is associated with nicotine withdrawal and the urge to smoke.
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SNPs was high in populations of European (r2=1, D′=1) and African (r2>0.66, D′>0.98) ancestry. Rs31746 was directly genotyped by all arrays used in the study. The effect of rs31746, as indicated by the magnitude and direction of the odds ratio, was consistent across the six studies that were included in the meta-analysis (Figure 2). The rs31746*A allele (EA frequency = 68%; AA frequency=47%) was associated with elevated risk for NicW (ORmeta =1.21 [95%CI 1.13–1.30]; P=3.67×10−8). The association of rs31746 to each individual DSM-IV NicW criterion for Yale-Penn 1 and Yale-Penn 2 subjects is shown in Table S2. Based on the EA+AA meta-analysis, the strongest associations were observed for “Did you feel down or depressed?” (Pmeta= 5×10−4), “Were you irritable, angry, or frustrated?” (Pmeta= 5×10−4) and “Were you restless?” (Pmeta= 1×10−3). The individual DSM NicW criterion data were unavailable for SAGE subjects.