Incorporating age at onset of smoking into genetic models for nicotine dependence: evidence for interaction with multiple genes.

Addiction Biology
Richard A GruczaLaura J Bierut

Abstract

Nicotine dependence is moderately heritable, but identified genetic associations explain only modest portions of this heritability. We analyzed 3369 SNPs from 349 candidate genes and investigated whether incorporation of SNP-by-environment interaction into association analyses might bolster gene discovery efforts and prediction of nicotine dependence. Specifically, we incorporated the interaction between allele count and age at onset of regular smoking (AOS) into association analyses of nicotine dependence. Subjects were from the Collaborative Genetic Study of Nicotine Dependence and included 797 cases ascertained for Fagerström nicotine dependence and 811 non-nicotine-dependent smokers as controls, all of European descent. Compared with main effect models, SNP x AOS interaction models resulted in higher numbers of nominally significant tests, increased predictive utility at individual SNPs and higher predictive utility in a multi-locus model. Some SNPs previously documented in main effect analyses exhibited improved fits in the joint analysis, including rs16969968 from CHRNA5 and rs2314379 from MAP3K4. CHRNA5 exhibited larger effects in later-onset smokers, in contrast with a previous report that suggested the opposite interac...Continue Reading

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Citations

Jul 19, 2012·Translational Psychiatry·A AgrawalM T Lynskey
Jan 14, 2012·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Ulla BromsAnu Loukola
May 1, 2012·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Jennifer J WareMarcus R Munafò
Aug 22, 2014·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Andrew W BergenGary E Swan
May 6, 2015·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·David J VandenberghCleve Redmond
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Oct 22, 2015·Big Data·Laura Bierut, David Cesarini
Jan 21, 2020·The American Journal on Addictions·Ni FanYufen Ou
Nov 10, 2020·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Christine AdjangbaLuke M Evans
Mar 7, 2021·Pharmacological Reports : PR·Nusrat Islam ChaityMohd Nazmul Hasan Apu

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