CHRNB3 is More Strongly Associated with Fagerström Test for Cigarette Dependence-based Nicotine Dependence Than Cigarettes Per Day: Phenotype Definition Changes Genome-wide Association Studies Results

Overview

Journal Addiction

Specialty Psychiatry

Date 2012 Apr 25

PMID 22524403

Citations 52

Authors

John P Rice

Sarah M Hartz

Arpana Agrawal

Laura Almasy

Siiri Bennett

Naomi Breslau

Kathleen K Bucholz

Kimberly F Doheny

Howard J Edenberg

Alison M Goate

Victor Hesselbrock

William B Howells

Eric O Johnson

John Kramer

Robert F Krueger

Samuel Kuperman

Cathy Laurie

Teri A Manolio

Rosalind J Neuman

John I Nurnberger

Bernice Porjesz

Elizabeth Pugh

Erin M Ramos

Nancy Saccone

Scott Saccone

Marc Schuckit

Laura J Bierut

Affiliations

Soon will be listed here.

Abstract

Aims: Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.e., CPD versus Fagerström test for cigarette dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence.

Design: Genome-wide association study.

Setting: Community sample.

Participants: A total of 3365 subjects who had smoked at least one cigarette were selected from the Study of Addiction: Genetics and Environment (SAGE). Of the participants, 2267 were European Americans, 999 were African Americans.

Measurements: Nicotine dependence defined by FTCD score ≥4, CPD.

Findings: The genetic locus most strongly associated with nicotine dependence was rs1451240 on chromosome 8 in the region of CHRNB3 [odds ratio (OR) = 0.65, P = 2.4 × 10(-8) ]. This association was further strengthened in a meta-analysis with a previously published data set (combined P = 6.7 × 10(-16) , total n = 4200). When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (β = -0.08, P = 0.0004).

Conclusions: Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence show different associations with polymorphisms in genetic loci.

Citing Articles

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Deutsch A, Selya A Addict Behav. 2020; 112:106571.

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