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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26239289
TITLE
Evidence of CNIH3 involvement in opioid dependence.
ABSTRACT
NlmCategory: UNASSIGNED
Opioid dependence, a severe addictive disorder and major societal problem, has been demonstrated to be moderately heritable. We conducted a genome-wide association study in Comorbidity and Trauma Study data comparing opioid-dependent daily injectors (N=1167) with opioid misusers who never progressed to daily injection (N=161). The strongest associations, observed for CNIH3 single-nucleotide polymorphisms (SNPs), were confirmed in two independent samples, the Yale-Penn genetic studies of opioid, cocaine and alcohol dependence and the Study of Addiction: Genetics and Environment, which both contain non-dependent opioid misusers and opioid-dependent individuals. Meta-analyses found five genome-wide significant CNIH3 SNPs. The A allele of rs10799590, the most highly associated SNP, was robustly protective (P=4.30E-9; odds ratio 0.64 (95% confidence interval 0.55-0.74)). Epigenetic annotation predicts that this SNP is functional in fetal brain. Neuroimaging data from the Duke Neurogenetics Study (N=312) provide evidence of this SNP's in vivo functionality; rs10799590 A allele carriers displayed significantly greater right amygdala habituation to threat-related facial expressions, a phenotype associated with resilience to psychopathology. Computational genetic analyses of physical dependence on morphine across 23 mouse strains yielded significant correlations for haplotypes in CNIH3 and functionally related genes. These convergent findings support CNIH3 involvement in the pathophysiology of opioid dependence, complementing prior studies implicating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate system.Molecular Psychiatry advance online publication, 4 August 2015; doi:10.1038/mp.2015.102.
DATE PUBLISHED
2015 Aug 4
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2015/01/14
revised 2015/05/12
accepted 2015/06/16
entrez 2015/08/05 06:00
pubmed 2015/08/05 06:00
medline 2015/08/05 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Nelson EC Nelson E C EC Department of Psychiatry, Washington University, St Louis, MO, USA.
Agrawal A Agrawal A A Department of Psychiatry, Washington University, St Louis, MO, USA.
Heath AC Heath A C AC Department of Psychiatry, Washington University, St Louis, MO, USA.
Bogdan R Bogdan R R Department of Psychiatry, Washington University, St Louis, MO, USA.
Sherva R Sherva R R Boston University School of Medicine, Boston, MA, USA.
Zhang B Zhang B B Department of Psychiatry, Washington University, St Louis, MO, USA.
Al-Hasani R Al-Hasani R R Department of Psychiatry, Washington University, St Louis, MO, USA.
Bruchas MR Bruchas M R MR Department of Psychiatry, Washington University, St Louis, MO, USA.
Chou YL Chou Y-L YL Department of Psychiatry, Washington University, St Louis, MO, USA.
Demers CH Demers C H CH Department of Psychiatry, Washington University, St Louis, MO, USA.
Carey CE Carey C E CE Department of Psychiatry, Washington University, St Louis, MO, USA.
Conley ED Conley E D ED 23andMe, Mountain View, CA, USA.
Fakira AK Fakira A K AK Columbia University College of Physicians and Surgeons, New York, NY, USA.
Farrer LA Farrer L A LA Boston University School of Medicine, Boston, MA, USA.
Goate A Goate A A Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Gordon S Gordon S S QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Henders AK Henders A K AK QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Hesselbrock V Hesselbrock V V University of Connecticut School of Medicine, Farmington, CT, USA.
Kapoor M Kapoor M M Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Lynskey MT Lynskey M T MT Institute of Psychiatry, King's College, London, UK.
Madden PA Madden P A F PA Department of Psychiatry, Washington University, St Louis, MO, USA.
Moron JA Moron J A JA Columbia University College of Physicians and Surgeons, New York, NY, USA.
Rice JP Rice J P JP Department of Psychiatry, Washington University, St Louis, MO, USA.
Saccone NL Saccone N L NL Department of Psychiatry, Washington University, St Louis, MO, USA.
Schwab SG Schwab S G SG Faculty of Science Medicine & Health, University of Wollongong, Wollongong, Australia.
Shand FL Shand F L FL Black Dog Institute, Sydney, Australia.
Todorov AA Todorov A A AA Department of Psychiatry, Washington University, St Louis, MO, USA.
Wallace L Wallace L L QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Wang T Wang T T Department of Psychiatry, Washington University, St Louis, MO, USA.
Wray NR Wray N R NR The University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia.
Zhou X Zhou X X St Jude Children's Research Hospital, Memphis, TN, USA.
Degenhardt L Degenhardt L L National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.
Martin NG Martin N G NG QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Hariri AR Hariri A R AR Duke University, Durham, NC, USA.
Kranzler HR Kranzler H R HR University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Gelernter J Gelernter J J Yale School of Medicine, New Haven, CT, USA.
Bierut LJ Bierut L J LJ Department of Psychiatry, Washington University, St Louis, MO, USA.
Clark DJ Clark D J DJ Stanford University School of Medicine, Stanford, CA, USA.
Montgomery GW Montgomery G W GW QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2015
MONTH: Aug
DAY: 4
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
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