Variation in the nicotinic acetylcholine receptor gene cluster CHRNA5-CHRNA3-CHRNB4 and its interaction with recent tobacco use influence cognitive flexibility.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Huiping ZhangJoel Gelernter

Abstract

Variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster have been associated with nicotine dependence (ND) and ND-related traits. To evaluate a potential underlying mechanism for this association, we investigated the effects of 10 variants in this gene cluster and their interactive effects as a result of recent smoking on cognitive flexibility, a possible mediator of genetic effects in smokers. Cognitive flexibility of 466 European Americans (EAs; 360 current smokers) and 805 African Americans (AAs; 635 current smokers) was assessed using the Wisconsin Card Sorting Test. The main effects of variants and haplotypes and their interaction with recent smoking on cognitive flexibility were examined using multivariate analysis of variance and the haplotype analysis program HAPSTAT. In EAs, the major alleles of five variants (CHRNA5-rs3841324-22 bp-insertion-allele, CHRNA5-rs615470-C-allele, CHRNA3-rs6495307-C-allele, CHRNA3-rs2869546-T-allele, and CHRNB4-rs11637890-C-allele) were associated with significantly greater perseverative responses (P=0.003-0.017) and perseverative errors (P=0.004-0.026; recessive effect). Among EAs homozygous for the major alleles of each of these five variants, current smokers made fewer perseverative responses ...Continue Reading

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Oct 11, 2011·Psychopharmacology·Suzanne H Mitchell, Vanessa B Wilson
Feb 1, 2012·Human Genetics·Allison B Gold, Caryn Lerman
Jan 23, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Margaret C WardleMarcus R Munafò
Jun 16, 2016·Journal of Psychiatric Research·Jaqueline B SchuchClaiton H D Bau
Oct 13, 2018·Journal of Neuroscience Research·Andrea B SchoteJobst Meyer
Apr 9, 2021·Frontiers in Behavioral Neuroscience·Yasmine SherafatChristie D Fowler

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