Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
23752247
TITLE
Genome-wide association study on detailed profiles of smoking behavior and nicotine dependence in a twin sample.
ABSTRACT
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 (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 (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.
DATE PUBLISHED
2014 May
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/06/18
revised 2013/03/28
accepted 2013/04/29
aheadofprint 2013/06/11
entrez 2013/06/12 06:00
pubmed 2013/06/12 06:00
medline 2015/01/20 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Loukola A Loukola A A Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland.
Wedenoja J Wedenoja J J Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland.
Keskitalo-Vuokko K Keskitalo-Vuokko K K Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland.
Broms U Broms U U 1] Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland [2] National Institute for Health and Welfare, Helsinki, Finland.
Korhonen T Korhonen T T 1] Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland [2] National Institute for Health and Welfare, Helsinki, Finland.
Ripatti S Ripatti S S 1] National Institute for Health and Welfare, Helsinki, Finland [2] Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland [3] Wellcome Trust Sanger Institute, Cambridge, UK.
Sarin AP Sarin A-P AP 1] National Institute for Health and Welfare, Helsinki, Finland [2] Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
Pitkäniemi J Pitkäniemi J J Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland.
He L He L L Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland.
Häppölä A Häppölä A A Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland.
Heikkilä K Heikkilä K K Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland.
Chou YL Chou Y-L YL Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Pergadia ML Pergadia M L ML Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Heath AC Heath A C AC Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Montgomery GW Montgomery G W GW Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Martin NG Martin N G NG Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Madden PA Madden P A F PA Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Kaprio J Kaprio J J 1] Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland [2] National Institute for Health and Welfare, Helsinki, Finland [3] Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
INVESTIGATORS
JOURNAL
VOLUME: 19
ISSUE: 5
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2014
MONTH: May
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AA011998 NIAAA NIH HHS United States
AA013320 NIAAA NIH HHS United States
AA013321 NIAAA NIH HHS United States
AA013326 NIAAA NIH HHS United States
AA017688 NIAAA NIH HHS United States
DA019951 NIDA NIH HHS United States
DA12854 NIDA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
K08 DA019951 NIDA NIH HHS United States
P60 AA011998 NIAAA NIH HHS United States
R01 AA013320 NIAAA NIH HHS United States
R01 AA013326 NIAAA NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Cohort Studies
Drug-Seeking Behavior
Family
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Linkage Disequilibrium
Male
Middle Aged
Phenotype
Receptor, ErbB-4 genetics
Smoking psychology
Tobacco Use Disorder psychology
Twins, Dizygotic genetics
Twins, Monozygotic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
EC 2.7.10.1 ERBB4 protein, human
EC 2.7.10.1 Receptor, ErbB-4
OTHER ID's
OTHERID SOURCE
NIHMS473933 NLM
PMC3883996 NLM