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Int J Mol Epidemiol Genet 2013;4(2):109-119

Original Article
Scrutiny of the CHRNA5-CHRNA3-CHRNB4 smoking behavior locus reveals a
novel association with alcohol use in a Finnish population based study

Jenni Hällfors, Anu Loukola, Janne Pitkäniemi, Ulla Broms, Satu Männistö, Veikko Salomaa, Markku Heliövaara, Terho
Lehtimäki, Olli Raitakari, Pamela AF Madden, Andrew C Heath, Grant W Montgomery, Nicholas G Martin, Tellervo Korhonen,
Jaakko Kaprio

Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland; Department of Public Health, Hjelt
Institute, Univer-sity of Helsinki, Helsinki, Finland; National Institute for Health and Welfare, Helsinki, Finland; Department of
Clinical Chemistry, Fimlab Laboratories, Tampere, Finland; Department of Clinical Chemistry, University of Tampere School of
Medicine, Tampere, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku,
Finland; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Department
of Psychiatry, Washington University School of Medicine, Saint Louis, USA; Queensland Institute of Medical Research,
Brisbane, Australia

Received June 20, 2013; Accepted June 20, 2013; Epub June 25, 2013; Published June 30, 2013

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. (IJMEG1306003).

Keywords: Nicotinic acetylcholine receptors, 15q25.1, alcohol use, smoking behavior, public health, population-based sample,
genetic association

Address correspondence to: Jenni Hällfors, Department of Public Health, Hjelt Institute, University of Helsinki, P. O. Box 41,
FI-00014 Univer-sity of Helsinki, Helsinki, Finland. Tel: +358919127598; Fax: +358919127600; E-mail: jenni.hallfors@helsinki.fi