title: Scrutiny of the CHRNA5-CHRNA3-CHRNB4 smoking behavior locus reveals a novel association with alcohol use in a Finnish population based study.
abstract: The CHRNA5-CHRNA3-CHRNB4 gene cluster on chromosome 15q25.1 encoding the cholinergic nicotinic receptor subunits is robustly associated with smoking behavior and nicotine dependence. Only a few studies to date have examined the locus with alcohol related traits and found evidence of association with alcohol abuse and dependence. Our main goal was to examine the role of three intensively studied single nucleotide polymorphisms, rs16969968, rs578776 and rs588765, tagging three distinct loci, in alcohol use. Our sample was drawn from two independent Finnish population-based surveys, the National FINRISK Study and the Health 2000 (Health Examination) Survey. The combined sample included a total of 32,592 adult Finns (54% women) of whom 8,356 were assessed for cigarettes per day (CPD). Data on alcohol use were available for 31,812 individuals. We detected a novel association between rs588765 and alcohol use defined as abstainers and low-frequency drinkers versus drinkers (OR=1.15, p=0.00007). Additionally, we provide precise estimates of strength of the association between the three loci and smoking quantity in a very large population based sample. As a conclusion, our results provide further evidence for the nicotine-specific role of rs16969968 (locus 1). Further, our data suggest that the effect of rs588765 (locus 3) may be specific to alcohol use as the effect is seen also in never smokers.
authors.affiliation: Institute for Molecular Medicine Finland FIMM, University of Helsinki Helsinki, Finland ; Department of Public Health, Hjelt Institute, University of Helsinki Helsinki, Finland.
authors.forename: Jenni
authors.initials: J
authors.lastname: Hällfors
authors.forename: Anu
authors.initials: A
authors.lastname: Loukola
authors.forename: Janne
authors.initials: J
authors.lastname: Pitkäniemi
authors.forename: Ulla
authors.initials: U
authors.lastname: Broms
authors.forename: Satu
authors.initials: S
authors.lastname: Männistö
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Markku
authors.initials: M
authors.lastname: Heliövaara
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Olli
authors.initials: O
authors.lastname: Raitakari
authors.forename: Pamela Af
authors.initials: PA
authors.lastname: Madden
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Heath
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Tellervo
authors.initials: T
authors.lastname: Korhonen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
keywords: 15q25.1; Nicotinic acetylcholine receptors; alcohol use; genetic association; population-based sample; public health; smoking behavior