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- W2212096717 abstract "Abstract We conducted a 1000 Genomes–imputed genome-wide association study (GWAS) meta-analysis for nicotine dependence, defined by the Fagerström Test for Nicotine Dependence in 17 074 ever smokers from five European-ancestry samples. We followed up novel variants in 7469 ever smokers from five independent European-ancestry samples. We identified genome-wide significant association in the alpha-4 nicotinic receptor subunit ( CHRNA4) gene on chromosome 20q13: lowest P =8.0 × 10 −9 across all the samples for rs2273500-C (frequency=0.15; odds ratio=1.12 and 95% confidence interval=1.08–1.17 for severe vs mild dependence). rs2273500-C, a splice site acceptor variant resulting in an alternate CHRNA4 transcript predicted to be targeted for nonsense-mediated decay, was associated with decreased CHRNA4 expression in physiologically normal human brains (lowest P =7.3 × 10 −4 ). Importantly, rs2273500-C was associated with increased lung cancer risk ( N =28 998, odds ratio=1.06 and 95% confidence interval=1.00–1.12), likely through its effect on smoking, as rs2273500-C was no longer associated with lung cancer after adjustment for smoking. Using criteria for smoking behavior that encompass more than the single ‘cigarettes per day’ item, we identified a common CHRNA4 variant with important regulatory properties that contributes to nicotine dependence and smoking-related consequences." @default.
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- W2212096717 date "2015-10-06" @default.
- W2212096717 modified "2023-09-26" @default.
- W2212096717 title "Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence" @default.
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