Genome-wide association study on detailed profiles of smoking behavior and nicotine dependence in a twin sample

Autor: Juho Wedenoja, Grant W. Montgomery, Antti-Pekka Sarin, Anja Häppölä, Anu Loukola, Nicholas G. Martin, Janne Pitkäniemi, Yi-Ling Chou, Jaakko Kaprio, Ulla Broms, Liang He, Andrew C. Heath, Michele L. Pergadia, Kauko Heikkilä, Samuli Ripatti, Pamela A. F. Madden, Kaisu Keskitalo-Vuokko, Tellervo Korhonen
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Male
Linkage disequilibrium
Candidate gene
Receptor
ErbB-4
medicine.medical_treatment
Population
Drug-Seeking Behavior
Single-nucleotide polymorphism
Genome-wide association study
Article
smoking behavior
Linkage Disequilibrium
Cohort Studies
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
smoking quantity
Neuregulin 3
medicine
Twins
Dizygotic
ADHD
Humans
Family
Genetic Predisposition to Disease
education
nicotine dependence
Molecular Biology
030304 developmental biology
Genetics
0303 health sciences
education.field_of_study
business.industry
Smoking
Tobacco Use Disorder
Twins
Monozygotic
Middle Aged
Twin study
3. Good health
schizophrenia
Psychiatry and Mental health
Phenotype
genome-wide association analysis
Smoking cessation
Female
business
030217 neurology & neurosurgery
Genome-Wide Association Study
Zdroj: Molecular psychiatry
ISSN: 1476-5578
1359-4184
Popis: Smoking is a major risk factor for several somatic diseases and is also emerging as a causal factor for neuropsychiatric disorders. Genome-wide association (GWA) and candidate gene studies for smoking behavior and nicotine dependence (ND) have disclosed too few predisposing variants to account for the high estimated heritability. Previous large-scale GWA studies have had very limited phenotypic definitions of relevance to smoking-related behavior, which has likely impeded the discovery of genetic effects. We performed GWA analyses on 1114 adult twins ascertained for ever smoking from the population-based Finnish Twin Cohort study. The availability of 17 smoking-related phenotypes allowed us to comprehensively portray the dimensions of smoking behavior, clustered into the domains of smoking initiation, amount smoked and ND. Our results highlight a locus on 16p12.3, with several single-nucleotide polymorphisms (SNPs) in the vicinity of CLEC19A showing association (Po1 � 10 � 6 ) with smoking quantity. Interestingly, CLEC19A is located close to a previously reported attention-deficit hyperactivity disorder (ADHD) linkage locus and an evident link between ADHD and smoking has been established. Intriguing preliminary association (Po1 � 10 � 5 ) was detected between DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) ND diagnosis and several SNPs in ERBB4, coding for a Neuregulin receptor, on 2q33. The association between ERBB4 and DSM-IV ND diagnosis was replicated in an independent Australian sample. Recently, a significant increase in ErbB4 and Neuregulin 3 (Nrg3) expression was revealed following chronic nicotine exposure and withdrawal in mice and an association between NRG3 SNPs and smoking cessation success was detected in a clinical trial. ERBB4 has previously been associated with schizophrenia; further, it is located within an established schizophrenia linkage locus and within a linkage locus for a smoker phenotype identified in this sample. In conclusion, we disclose novel tentative evidence for the involvement of ERBB4 in ND, suggesting the involvement of the Neuregulin/ErbB signalling pathway in addictions and providing a plausible link between the high co-morbidity of schizophrenia and ND.
Databáze: OpenAIRE
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