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Genome-wide association study on detailed profiles of smoking behavior and nicotine dependence in a twin sample
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883996/ https://www.ncbi.nlm.nih.gov/pubmed/23752247 http://dx.doi.org/10.1038/mp.2013.72 |
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author | Loukola, Anu Wedenoja, Juho Keskitalo-Vuokko, Kaisu Broms, Ulla Korhonen, Tellervo Ripatti, Samuli Sarin, Antti-Pekka Pitkäniemi, Janne He, Liang Häppölä, Anja Heikkilä, Kauko Chou, Yi-Ling Pergadia, Michele L Heath, Andrew C Montgomery, Grant W Martin, Nicholas G Madden, Pamela AF Kaprio, Jaakko |
author_facet | Loukola, Anu Wedenoja, Juho Keskitalo-Vuokko, Kaisu Broms, Ulla Korhonen, Tellervo Ripatti, Samuli Sarin, Antti-Pekka Pitkäniemi, Janne He, Liang Häppölä, Anja Heikkilä, Kauko Chou, Yi-Ling Pergadia, Michele L Heath, Andrew C Montgomery, Grant W Martin, Nicholas G Madden, Pamela AF Kaprio, Jaakko |
author_sort | Loukola, Anu |
collection | PubMed |
description | 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. Prior 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 genome-wide association 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 SNPs in the vicinity of CLEC19A showing association (P<1×10(−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 (P<1×10(−5)) was detected between DSM-IV 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. Interestingly, in the paper by Turner et al., significant increase in ErbB4 and Neuregulin 3 (Nrg3) expression was revealed following chronic nicotine exposure and withdrawal in mice. Turner et al. also detected an association between NRG3 SNPs and smoking cessation success 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. As a 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. |
format | Online Article Text |
id | pubmed-3883996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-38839962014-11-01 Genome-wide association study on detailed profiles of smoking behavior and nicotine dependence in a twin sample Loukola, Anu Wedenoja, Juho Keskitalo-Vuokko, Kaisu Broms, Ulla Korhonen, Tellervo Ripatti, Samuli Sarin, Antti-Pekka Pitkäniemi, Janne He, Liang Häppölä, Anja Heikkilä, Kauko Chou, Yi-Ling Pergadia, Michele L Heath, Andrew C Montgomery, Grant W Martin, Nicholas G Madden, Pamela AF Kaprio, Jaakko Mol Psychiatry Article 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. Prior 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 genome-wide association 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 SNPs in the vicinity of CLEC19A showing association (P<1×10(−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 (P<1×10(−5)) was detected between DSM-IV 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. Interestingly, in the paper by Turner et al., significant increase in ErbB4 and Neuregulin 3 (Nrg3) expression was revealed following chronic nicotine exposure and withdrawal in mice. Turner et al. also detected an association between NRG3 SNPs and smoking cessation success 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. As a 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. 2013-06-11 2014-05 /pmc/articles/PMC3883996/ /pubmed/23752247 http://dx.doi.org/10.1038/mp.2013.72 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Loukola, Anu Wedenoja, Juho Keskitalo-Vuokko, Kaisu Broms, Ulla Korhonen, Tellervo Ripatti, Samuli Sarin, Antti-Pekka Pitkäniemi, Janne He, Liang Häppölä, Anja Heikkilä, Kauko Chou, Yi-Ling Pergadia, Michele L Heath, Andrew C Montgomery, Grant W Martin, Nicholas G Madden, Pamela AF Kaprio, Jaakko Genome-wide association study on detailed profiles of smoking behavior and nicotine dependence in a twin sample |
title | Genome-wide association study on detailed profiles of smoking
behavior and nicotine dependence in a twin sample |
title_full | Genome-wide association study on detailed profiles of smoking
behavior and nicotine dependence in a twin sample |
title_fullStr | Genome-wide association study on detailed profiles of smoking
behavior and nicotine dependence in a twin sample |
title_full_unstemmed | Genome-wide association study on detailed profiles of smoking
behavior and nicotine dependence in a twin sample |
title_short | Genome-wide association study on detailed profiles of smoking
behavior and nicotine dependence in a twin sample |
title_sort | genome-wide association study on detailed profiles of smoking
behavior and nicotine dependence in a twin sample |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883996/ https://www.ncbi.nlm.nih.gov/pubmed/23752247 http://dx.doi.org/10.1038/mp.2013.72 |
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