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

John P Rice; Sarah M Hartz; Arpana Agrawal; Laura Almasy; Siiri Bennett; Naomi Breslau; Kathleen K Bucholz; Gene Environment Association Studies Consortium; 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; GENEVA Consortium

doi:10.1111/j.1360-0443.2012.03922.x

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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

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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

John P Rice, Sarah M Hartz, Arpana Agrawal, Laura Almasy, Siiri Bennett, Naomi Breslau, Kathleen K Bucholz, Gene Environment Association Studies Consortium, Howard J Edenberg, Alison M Goate, …

Addiction (Abingdon, England), Vol.107(11), pp.2019-2028

11/2012

DOI: 10.1111/j.1360-0443.2012.03922.x

PMCID: PMC3427406

PMID: 22524403

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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.

genome‐wide association studies

CHRNB3

meta‐analysis

phenotype definitions

Details

Title: Subtitle: 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
Creators: John P Rice - Washington University School of Medicine
Sarah M Hartz - Washington University School of Medicine
Arpana Agrawal - Washington University School of Medicine
Laura Almasy - Southwest Foundation for Biomedical Research
Siiri Bennett - University of Washington
Naomi Breslau - Michigan State University
Kathleen K Bucholz - Washington University School of Medicine
Gene Environment Association Studies Consortium
Howard J Edenberg - Indiana University School of Medicine
Alison M Goate - Washington University School of Medicine
Victor Hesselbrock - University of Connecticut
William B Howells - Washington University School of Medicine
Eric O Johnson - Research Triangle Institute International
John Kramer - University of Iowa College of Medicine
Robert F Krueger - University of Minnesota
Samuel Kuperman - University of Iowa Hospitals
Cathy Laurie - University of Washington
Teri A Manolio - National Human Genome Research Institute
Rosalind J Neuman - Washington University School of Medicine
John I Nurnberger - Indiana University School of Medicine
Bernice Porjesz - State University of New York
Elizabeth Pugh - Johns Hopkins School of Medicine
Erin M Ramos - National Human Genome Research Institute
Nancy Saccone - Washington University School of Medicine
Scott Saccone - Washington University School of Medicine
Marc Schuckit - University of California–San Diego
Laura J Bierut - Washington University School of Medicine
GENEVA Consortium
Resource Type: Journal article
Publication Details: Addiction (Abingdon, England), Vol.107(11), pp.2019-2028
DOI: 10.1111/j.1360-0443.2012.03922.x
PMID: 22524403
PMCID: PMC3427406
NLM abbreviation: Addiction
ISSN: 0965-2140
eISSN: 1360-0443
Number of pages: 10
Grant note: National Institute on Drug Abuse NIH (HHSN268200782096C; UL1RR024992; K02DA021237; UL1RR024992; KL2RR024994; T32MH014677) National Institute on Alcohol Abuse and Alcoholism NIH Genes, Environment and Health Initiative (GEI) (U01HG004422; U01HG004438) National Cancer Institute (P01 CA089392)
Language: English
Date published: 11/2012
Academic Unit: Psychiatry; Stead Family Department of Pediatrics
Record Identifier: 9984003453302771

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