Genome-Wide Meta-Analysis of Cotinine Levels in Cigarette Smokers Identifies Locus at

Genome-wide association studies (GWAS) of complex behavioural phenotypes such as cigarette smoking typically employ self-report phenotypes. However, precise biomarker phenotypes may afford greater statistical power and identify novel variants. Here we report the results of a GWAS meta-analysis of levels of cotinine, the primary metabolite of nicotine, in 4,548 daily smokers of European ancestry. We identified a locus close to UGT2B10 at 4q13.2 (minimum p = 5.89 × 10 − 10 for rs114612145), high linkage disequilibrium a known functional variant in the UGT2B10 nicotine and cotinine glucuronidation activity, nicotine we observed association between multiple variants within the 15q25.1 region and cotinine levels, all within the CHRNA5-A3-B4 gene cluster or adjacent genes, with previous much larger GWAS using self-report measures of smoking quantity. using precise biomarker measures in that

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