Journal Article

Variants Located Upstream of CHRNB4 on Chromosome 15q25.1 Are Associated with Age at Onset of Daily Smoking and Habitual Smoking

Kapoor, Manav, Budde, John P., Goate, Alison M., Foroud, Tatiana, Kuperman, Samuel, Rice, John, Porjesz, Bernice, Edenberg, Howard J., Bertelsen, Sarah, Agrawal, Arpana, Hesselbrock, Victor, Kramer, John, Tischfield, Jay, Dick, Danielle, Xuei, Xiaoling, Brooks, Andrew, Manz, Niklas, Wang, Jen-Chyong, Hinrichs, Anthony, Schuckit, Marc, Bucholz, Kathy, Chorlian, David, Nurnberger, John, Bierut, Laura J.

2012

Overview

Several genome-wide association and candidate gene studies have linked chromosome 15q24-q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking the CHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were recruited from families affected with alcoholism (either as a first or second degree relative) and the comparison families. Participants completed the SSAGA interview, a comprehensive assessment of alcohol and other substance use and related behaviors. Using the Quantitative trait disequilibrium test (QTDT) significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. Multivariate analysis using a Cox proportional hazards model further revealed that these variants significantly predict the age at onset of habitual smoking among daily smokers. These variants were not in high linkage disequilibrium (0.28

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Addictions / Addictive behaviors / Adolescent / Adolescents / Adult / Adults / Age / Age of Onset / Alcoholic beverages / Alcoholism / Alcoholism - genetics / Amino acids / Analysis / Behavior / Behavioral sciences / Biochemistry / Biology / Chromosome 15 / Chromosomes, Human, Pair 15 - genetics / Chronic obstructive lung disease / Chronic obstructive pulmonary disease / Cigarettes / Clusters / Cross-Sectional Studies / Disorders / Drug abuse / Drug dependence / Drug therapy / Family / Female / Genes / Genetic aspects / Genetic Predisposition to Disease / Genetics / Genomes / Genomics / Hazards / Health risk assessment / Humans / Illnesses / Juvenile drug abuse / Linkage Disequilibrium / Lung cancer / Lung diseases / Male / Medicine / Mental disorders / Molecular biology / Multigene Family / Multivariate analysis / Nerve Tissue Proteins - genetics / Neurosciences / Nicotine / Obstructive lung disease / Polymorphism, Single Nucleotide / Proportional Hazards Models / Psychiatrists / Psychiatry / Receptors, Nicotinic - genetics / Risk Factors / Secondary school students / Single-nucleotide polymorphism / Smokers / Smoking / Smoking - genetics / Smoking - psychology / Smoking cessation / Social and Behavioral Sciences / Statistical models / Studies / Substance use / Teenagers / Tobacco / Young Adult / Young adults / Youth / Youth smoking