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Evidence of CNIH3 involvement in opioid dependence.

Publication ,  Journal Article
Nelson, EC; Agrawal, A; Heath, AC; Bogdan, R; Sherva, R; Zhang, B; Al-Hasani, R; Bruchas, MR; Chou, Y-L; Demers, CH; Carey, CE; Conley, ED ...
Published in: Molecular psychiatry
May 2016

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.

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Published In

Molecular psychiatry

DOI

EISSN

1476-5578

ISSN

1359-4184

Publication Date

May 2016

Volume

21

Issue

5

Start / End Page

608 / 614

Related Subject Headings

  • Young Adult
  • Species Specificity
  • Receptors, AMPA
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Opioid-Related Disorders
  • Mice, Inbred Strains
  • Male
  • Humans
  • Habituation, Psychophysiologic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Nelson, E. C., Agrawal, A., Heath, A. C., Bogdan, R., Sherva, R., Zhang, B., … Montgomery, G. W. (2016). Evidence of CNIH3 involvement in opioid dependence. Molecular Psychiatry, 21(5), 608–614. https://doi.org/10.1038/mp.2015.102
Nelson, E. C., A. Agrawal, A. C. Heath, R. Bogdan, R. Sherva, B. Zhang, R. Al-Hasani, et al. “Evidence of CNIH3 involvement in opioid dependence.Molecular Psychiatry 21, no. 5 (May 2016): 608–14. https://doi.org/10.1038/mp.2015.102.
Nelson EC, Agrawal A, Heath AC, Bogdan R, Sherva R, Zhang B, et al. Evidence of CNIH3 involvement in opioid dependence. Molecular psychiatry. 2016 May;21(5):608–14.
Nelson, E. C., et al. “Evidence of CNIH3 involvement in opioid dependence.Molecular Psychiatry, vol. 21, no. 5, May 2016, pp. 608–14. Epmc, doi:10.1038/mp.2015.102.
Nelson EC, Agrawal A, Heath AC, Bogdan R, Sherva R, Zhang B, Al-Hasani R, Bruchas MR, Chou Y-L, Demers CH, Carey CE, Conley ED, Fakira AK, Farrer LA, Goate A, Gordon S, Henders AK, Hesselbrock V, Kapoor M, Lynskey MT, Madden PAF, Moron JA, Rice JP, Saccone NL, Schwab SG, Shand FL, Todorov AA, Wallace L, Wang T, Wray NR, Zhou X, Degenhardt L, Martin NG, Hariri AR, Kranzler HR, Gelernter J, Bierut LJ, Clark DJ, Montgomery GW. Evidence of CNIH3 involvement in opioid dependence. Molecular psychiatry. 2016 May;21(5):608–614.

Published In

Molecular psychiatry

DOI

EISSN

1476-5578

ISSN

1359-4184

Publication Date

May 2016

Volume

21

Issue

5

Start / End Page

608 / 614

Related Subject Headings

  • Young Adult
  • Species Specificity
  • Receptors, AMPA
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Opioid-Related Disorders
  • Mice, Inbred Strains
  • Male
  • Humans
  • Habituation, Psychophysiologic