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Genome-wide association study identifies a novel locus for cannabis dependence.

Publication ,  Journal Article
Agrawal, A; Chou, Y-L; Carey, CE; Baranger, DAA; Zhang, B; Sherva, R; Wetherill, L; Kapoor, M; Wang, J-C; Bertelsen, S; Anokhin, AP; Kramer, J ...
Published in: Molecular psychiatry
May 2018

Despite moderate heritability, only one study has identified genome-wide significant loci for cannabis-related phenotypes. We conducted meta-analyses of genome-wide association study data on 2080 cannabis-dependent cases and 6435 cannabis-exposed controls of European descent. A cluster of correlated single-nucleotide polymorphisms (SNPs) in a novel region on chromosome 10 was genome-wide significant (lowest P=1.3E-8). Among the SNPs, rs1409568 showed enrichment for H3K4me1 and H3K427ac marks, suggesting its role as an enhancer in addiction-relevant brain regions, such as the dorsolateral prefrontal cortex and the angular and cingulate gyri. This SNP is also predicted to modify binding scores for several transcription factors. We found modest evidence for replication for rs1409568 in an independent cohort of African American (896 cases and 1591 controls; P=0.03) but not European American (EA; 781 cases and 1905 controls) participants. The combined meta-analysis (3757 cases and 9931 controls) indicated trend-level significance for rs1409568 (P=2.85E-7). No genome-wide significant loci emerged for cannabis dependence criterion count (n=8050). There was also evidence that the minor allele of rs1409568 was associated with a 2.1% increase in right hippocampal volume in an independent sample of 430 EA college students (fwe-P=0.008). The identification and characterization of genome-wide significant loci for cannabis dependence is among the first steps toward understanding the biological contributions to the etiology of this psychiatric disorder, which appears to be rising in some developed nations.

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Published In

Molecular psychiatry

DOI

EISSN

1476-5578

ISSN

1359-4184

Publication Date

May 2018

Volume

23

Issue

5

Start / End Page

1293 / 1302

Related Subject Headings

  • Young Adult
  • White People
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Middle Aged
  • Marijuana Abuse
  • Male
  • Humans
  • Genotype
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Agrawal, A., Chou, Y.-L., Carey, C. E., Baranger, D. A. A., Zhang, B., Sherva, R., … Nelson, E. C. (2018). Genome-wide association study identifies a novel locus for cannabis dependence. Molecular Psychiatry, 23(5), 1293–1302. https://doi.org/10.1038/mp.2017.200
Agrawal, A., Y. -. L. Chou, C. E. Carey, D. A. A. Baranger, B. Zhang, R. Sherva, L. Wetherill, et al. “Genome-wide association study identifies a novel locus for cannabis dependence.Molecular Psychiatry 23, no. 5 (May 2018): 1293–1302. https://doi.org/10.1038/mp.2017.200.
Agrawal A, Chou Y-L, Carey CE, Baranger DAA, Zhang B, Sherva R, et al. Genome-wide association study identifies a novel locus for cannabis dependence. Molecular psychiatry. 2018 May;23(5):1293–302.
Agrawal, A., et al. “Genome-wide association study identifies a novel locus for cannabis dependence.Molecular Psychiatry, vol. 23, no. 5, May 2018, pp. 1293–302. Epmc, doi:10.1038/mp.2017.200.
Agrawal A, Chou Y-L, Carey CE, Baranger DAA, Zhang B, Sherva R, Wetherill L, Kapoor M, Wang J-C, Bertelsen S, Anokhin AP, Hesselbrock V, Kramer J, Lynskey MT, Meyers JL, Nurnberger JI, Rice JP, Tischfield J, Bierut LJ, Degenhardt L, Farrer LA, Gelernter J, Hariri AR, Heath AC, Kranzler HR, Madden PAF, Martin NG, Montgomery GW, Porjesz B, Wang T, Whitfield JB, Edenberg HJ, Foroud T, Goate AM, Bogdan R, Nelson EC. Genome-wide association study identifies a novel locus for cannabis dependence. Molecular psychiatry. 2018 May;23(5):1293–1302.

Published In

Molecular psychiatry

DOI

EISSN

1476-5578

ISSN

1359-4184

Publication Date

May 2018

Volume

23

Issue

5

Start / End Page

1293 / 1302

Related Subject Headings

  • Young Adult
  • White People
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Middle Aged
  • Marijuana Abuse
  • Male
  • Humans
  • Genotype