|
|
| PMID |
|
|
| 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 |
|
|
| 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 |
| Cites |
Behav Genet. 2011 Jul;41(4):512-21 |
20953688 |
|
| Cites |
Biol Psychiatry. 2011 Sep 15;70(6):513-8 |
21529783 |
|
| Cites |
Nat Rev Genet. 2011 Oct;12(10):703-14 |
21921926 |
|
| Cites |
Thorax. 2011 Oct;66(10):894-902 |
21685187 |
|
| Cites |
Mol Psychiatry. 2012 Jan;17(1):2-3 |
21826059 |
|
| Cites |
Am J Hum Genet. 2012 Jan 13;90(1):7-24 |
22243964 |
|
| Cites |
Hum Genet. 2012 Jun;131(6):1009-21 |
22006218 |
|
| Cites |
J Natl Cancer Inst. 2012 May 16;104(10):740-8 |
22534784 |
|
| Cites |
Nicotine Tob Res. 2012 Jun;14(6):720-33 |
22241830 |
|
| Cites |
J Stud Alcohol Drugs. 2012 Sep;73(5):820-8 |
22846246 |
|
| Cites |
Arch Gen Psychiatry. 2012 Aug;69(8):854-60 |
22868939 |
|
| Cites |
Psychol Med. 2011 Dec;41(12):2615-23 |
21733216 |
|
| Cites |
Nat Genet. 2010 May;42(5):441-7 |
20418890 |
|
| Cites |
Genet Epidemiol. 2008 Apr;32(3):227-34 |
18300295 |
|
| Cites |
Nature. 2008 Apr 3;452(7187):633-7 |
18385738 |
|
| Cites |
Nature. 2008 Apr 3;452(7187):638-42 |
18385739 |
|
| Cites |
Mol Psychiatry. 2008 May;13(5):522-30 |
18301393 |
|
| Cites |
Genet Epidemiol. 2008 May;32(4):381-5 |
18348202 |
|
| Cites |
Nat Genet. 2008 May;40(5):616-22 |
18385676 |
|
| Cites |
Pharmacogenomics J. 2008 Jun;8(3):209-19 |
17549066 |
|
| Cites |
Arch Gen Psychiatry. 2008 Jun;65(6):683-93 |
18519826 |
|
| Cites |
Am J Psychiatry. 2008 Sep;165(9):1163-71 |
18519524 |
|
| Cites |
MMWR Morb Mortal Wkly Rep. 2008 Nov 14;57(45):1226-8 |
19008791 |
|
| Cites |
Mol Med. 2009 Jan-Feb;15(1-2):21-7 |
19009022 |
|
| Cites |
PLoS One. 2009;4(2):e4653 |
19247474 |
|
| Cites |
Am J Hum Genet. 2009 Mar;84(3):367-79 |
19268276 |
|
| Cites |
Am J Hum Genet. 2002 May;70(5):1183-96 |
11923911 |
|
| Cites |
Cell. 2003 Jan 10;112(1):63-75 |
12526794 |
|
| Cites |
Twin Res. 2002 Oct;5(5):358-65 |
12537859 |
|
| Cites |
Am J Hum Genet. 2003 May;72(5):1268-79 |
12687500 |
|
| Cites |
Addict Behav. 2003 Aug;28(6):1149-57 |
12834657 |
|
| Cites |
Am J Hum Genet. 2004 Apr;74(4):765-9 |
14997420 |
|
| Cites |
Nicotine Tob Res. 2004 Apr;6(2):327-48 |
15203807 |
|
| Cites |
Br J Psychiatry. 2010 Jun;196(6):425-6 |
20513848 |
|
| Cites |
Hum Mol Genet. 2004 Aug 15;13(16):1693-702 |
15198991 |
|
| Cites |
PLoS Genet. 2009 Jun;5(6):e1000529 |
19543373 |
|
| Cites |
Mol Psychiatry. 2009 Jul;14(7):668-80 |
19188921 |
|
| Cites |
Mol Psychiatry. 2009 Aug;14(8):774-85 |
19349958 |
|
| Cites |
Hum Mol Genet. 2009 Oct 15;18(20):4007-12 |
19628476 |
|
| Cites |
Biol Psychiatry. 2010 Jan 1;67(1):12-9 |
19819424 |
|
| Cites |
Twin Res Hum Genet. 2010 Feb;13(1):10-29 |
20158304 |
|
| Cites |
Nat Genet. 2010 May;42(5):448-53 |
20418888 |
|
| Cites |
Nat Genet. 2010 May;42(5):436-40 |
20418889 |
|
| Cites |
Behav Brain Res. 2004 Aug 12;153(1):159-70 |
15219717 |
|
| Cites |
Nat Rev Genet. 2000 Dec;1(3):182-90 |
11252747 |
|
| Cites |
Nicotine Tob Res. 2001 Nov;3(4):353-9 |
11694203 |
|
| Cites |
Hum Mol Genet. 2001 Dec 15;10(26):3037-48 |
11751686 |
|
| Cites |
Addict Behav. 2002 Jan-Feb;27(1):101-13 |
11800217 |
|
| Cites |
Br J Addict. 1991 Sep;86(9):1119-27 |
1932883 |
|
| Cites |
Br J Psychiatry. 1991 Nov;159:653-8 |
1756341 |
|
| Cites |
J Stud Alcohol. 1994 Mar;55(2):149-58 |
8189735 |
|
| Cites |
Schizophr Bull. 1994;20(1):191-201 |
8197415 |
|
| Cites |
Neuron. 1997 Jun;18(6):847-55 |
9208852 |
|
| Cites |
Bioinformatics. 2005 Jan 15;21(2):263-5 |
15297300 |
|
| Cites |
Nat Neurosci. 2005 Nov;8(11):1465-70 |
16251989 |
|
| Cites |
Addict Behav. 2006 Jan;31(1):133-6 |
15922514 |
|
| Cites |
Am J Med Genet B Neuropsychiatr Genet. 2006 Jan 5;141B(1):96-101 |
16249994 |
|
| Cites |
Am J Med Genet B Neuropsychiatr Genet. 2006 Mar 5;141B(2):142-8 |
16402353 |
|
| Cites |
Nat Genet. 2006 May;38(5):556-60 |
16582909 |
|
| Cites |
Nicotine Tob Res. 2006 Jun;8(3):339-51 |
16801292 |
|
| Cites |
Nat Med. 2006 Jul;12(7):824-8 |
16767099 |
|
| Cites |
Mol Psychiatry. 2006 Dec;11(12):1062-5 |
17130882 |
|
| Cites |
Hum Mol Genet. 2007 Jan 1;16(1):24-35 |
17158188 |
|
| Cites |
Hum Mol Genet. 2007 Jan 15;16(2):129-41 |
17164265 |
|
| Cites |
Am J Hum Genet. 2007 May;80(5):856-66 |
17436240 |
|
| Cites |
BMC Genet. 2007;8:10 |
17407593 |
|
| Cites |
Drug Alcohol Depend. 2007 Jun 15;89(1):42-51 |
17174039 |
|
| Cites |
Am J Hum Genet. 2007 Sep;81(3):559-75 |
17701901 |
|
| Cites |
Addiction. 2008 Jan;103(1):162-71 |
18031565 |
|
| Cites |
Br J Psychiatry. 2010 Jun;196(6):440-6 |
20513853 |
|
| Cites |
N Engl J Med. 2010 Jun 17;362(24):2295-303 |
20554984 |
|
| Cites |
Am J Hum Genet. 2010 Jul 9;87(1):139-45 |
20598278 |
|
| Cites |
PLoS Genet. 2010 Aug;6(8). pii: e1001053. doi: 10.1371/journal.pgen.1001053 |
20700436 |
|
| Cites |
Genome Res. 2010 Oct;20(10):1344-51 |
20810666 |
|
| Cites |
Nature. 2010 Dec 23;468(7327):1061-6 |
21179162 |
|
| Cites |
Psychiatry Res. 2011 Feb 28;191(2):133-7 |
21232925 |
|
| Cites |
Nature. 2011 Mar 31;471(7340):597-601 |
21278726 |
|
|
| 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 |
|
|
