TY - JOUR
T1 - Scrutiny of the CHRNA5-CHRNA3-CHRNB4 smoking behavior locus reveals a novel association with alcohol use in a Finnish population based study
AU - Hällfors, Jenni
AU - Loukola, Anu
AU - Pitkäniemi, Janne
AU - Broms, Ulla
AU - Männistö, Satu
AU - Salomaa, Veikko
AU - Heliövaara, Markku
AU - Lehtimäki, Terho
AU - Raitakari, Olli
AU - Madden, Pamela A.F.
AU - Heath, Andrew C.
AU - Montgomery, Grant W.
AU - Martin, Nicholas G.
AU - Korhonen, Tellervo
AU - Kaprio, Jaakko
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - 15q25.1
KW - Alcohol use
KW - Genetic association
KW - Nicotinic acetylcholine receptors
KW - Population-based sample
KW - Public health
KW - Smoking behavior
UR - http://www.scopus.com/inward/record.url?scp=84879988890&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:84879988890
SN - 1948-1756
VL - 4
SP - 109
EP - 119
JO - International Journal of Molecular Epidemiology and Genetics
JF - International Journal of Molecular Epidemiology and Genetics
IS - 2
ER -