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

Agrawal, A., Chou, Y.- L., Carey, C. E., Baranger, D. A. A., Zhang, B., Sherva, R., Wetherill, L., Kapoor, M., Wang, J.-.C., Bertelsen, S., Anokhin, A. P., Hesselbrock, V., Kramer, J., Lynskey, M. T., Meyers, J. L., Nurnberger, J. I., Rice, J. P., Tischfield, J., Bierut, L. J., Degenhardt, L., Farrer, L. A., Gelernter, J., Hariri, A. R., Heath, A. C., Kranzler, H. R., Madden, P. A. F., Martin, N. G., Montgomery, G. W., Porjesz, B., Wang, T., Whitfield, J. B., Edenberg, H. J., Foroud, T., Goate, A. M., Bogdan, R. and Nelson, E. C. (2017) Genome-wide association study identifies a novel locus for cannabis dependence. Molecular Psychiatry, 23 5: 1293-1302. doi:10.1038/mp.2017.200

Author Agrawal, A.
Chou, Y.- L.
Carey, C. E.
Baranger, D. A. A.
Zhang, B.
Sherva, R.
Wetherill, L.
Kapoor, M.
Wang, J.-.C.
Bertelsen, S.
Anokhin, A. P.
Hesselbrock, V.
Kramer, J.
Lynskey, M. T.
Meyers, J. L.
Nurnberger, J. I.
Rice, J. P.
Tischfield, J.
Bierut, L. J.
Degenhardt, L.
Farrer, L. A.
Gelernter, J.
Hariri, A. R.
Heath, A. C.
Kranzler, H. R.
Madden, P. A. F.
Martin, N. G.
Montgomery, G. W.
Porjesz, B.
Wang, T.
Whitfield, J. B.
Edenberg, H. J.
Foroud, T.
Goate, A. M.
Bogdan, R.
Nelson, E. C.
Title Genome-wide association study identifies a novel locus for cannabis dependence
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1476-5578
Publication date 2017-11-07
Year available 2017
Sub-type Article (original research)
DOI 10.1038/mp.2017.200
Open Access Status PMC
Volume 23
Issue 5
Start page 1293
End page 1302
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract 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.Molecular Psychiatry advance online publication, 7 November 2017; doi:10.1038/mp.2017.200.
Keyword Alcohol-Dependence
Partitioning Heritability
Endocannabinoid System
Common Disease
Use Initiation
Use Disorder
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID RC2 DA028909
P50 MH096891
R01 AA007535
K02 DA032573
U01 HG004438
T32 GM008151
R01 AG049789
K05 AA017688
R37 MH057881
U01 HG004446
R01 DA012690
N01 HG065403
R01 DA006227
P60 AA011998
R01 DA012849
R01 DA033369
R01 MH101782
R01 MH075916
R01 MH101810
R01 DA023668
R01 MH101819
K01 DA037914
R01 DA033684
R01 MH090936
R01 MH057881
R01 MH101584
R01 AA013321
R01 DA018432
U01 HG004422
R01 DA019963
R01 DA036583
P50 MH084053
P30 CA091842
R01 MH097276
R01 AA011330
R01 DA012854
R01 MH090951
R01 AA017535
R01 MH093725
P50 AG005138
UL1 TR000448
K08 DA019951
R01 AG045231
R01 DA017305
R01 MH101820
R01 MH101825
R01 MH090941
U10 AA008401
R37 AA007728
R01 HD083614
R01 MH101822
R01 MH090937
R01 MH080405
UL1 TR002345
R01 MH101814
R01 MH085542
R01 AA013320
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
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Created: Wed, 15 Nov 2017, 12:02:31 EST