CHRNB 3 is more strongly associated with F agerström T est for C igarette D ependence‐based nicotine dependence than cigarettes per day: phenotype definition changes genome‐wide association studies results
Year: 2012
Type: article
Study design: Observational Study
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.
Source: Addiction
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
Institutions: Washington University in St. Louis, Texas Biomedical Research Institute, University of Washington, Michigan State University, Johns Hopkins University, Johns Hopkins Medicine, Indiana University Indianapolis, Indiana University School of Medicine, University of Connecticut, UConn Health, RTI International, University of Iowa, University of Iowa Health Care, University of Minnesota, University of Iowa Hospitals and Clinics, National Human Genome Research Institute, State University of New York, SUNY Downstate Health Sciences University, University of California San Diego
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Pfizer, Johns Hopkins University, National Institutes of Health, U.S. Public Health Service, National Institute on Alcohol Abuse and Alcoholism, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, National Cancer Institute, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1083756078, G1270179341, G1921953589, G2146332128, G2196166416, G2202404319, Study of Addiction: Genetics and Environment, Washington University Institute of Clinical and Translational Sciences, G3245180032, G363841575, G370871742, G3799582765, G407586344, G413336477, G4418141037, G4503763930, Genome Wide Association Coordinating Center, G5184311545, FAMILY STUDY OF COCAINE DEPENDENCE, G7093047072, Washington University Institute of Clinical and Translational Sciences, G7522350138, Washington University Institute of Clinical and Translational Sciences (KL2), G7755649354, G8267674335, G858805679, G8924909668, G8934415930, G9000024769, G9000025954, G9000054071, G9000083019, G9000134904, G9000176579
OpenAlex ID: W2121284248