期刊
MOLECULAR PSYCHIATRY
卷 23, 期 5, 页码 1293-1302出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2017.200
关键词
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资金
- National Institute on Drug Abuse (NIDA) [K02DA032573, R01DA023668]
- National Science Foundation [DGE-1143954]
- Mr and Mrs Spencer T Olin Fellowship Program
- NIMH [T32-GM008151]
- NSF [DGE-1745038]
- Australian National Health and Medical Research Council (NHMRC) Principal Research Fellowship [1041472]
- National Institutes of Health [R01-AG045231, R01-HD083614, U01-AG052564, N01-HG-65403]
- National Institute on Alcohol Abuse and Alcoholism
- NIH GEI [U01HG004438]
- NIH contract 'High throughput genotyping for studying the genetic contributions to human disease' [HHSN268200782096C]
- NCI Cancer Center Support Grant [P30 CA91842]
- ICTS/CTSA Grant from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1RR024992]
- NIH Roadmap for Medical Research
- NIH from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) [U10AA008401]
- National Institute on Drug Abuse (NIDA)
- National Institute on Drug Abuse [R01 DA17305, DA033369]
- Australian Government under the Substance Misuse Prevention and Service Improvements Grants Fund
- NIH Genes, Environment and Health Initiative (GEI) [U01 HG004422]
- Gene Environment Association Studies (GENEVA) under GEI
- GENEVA Coordinating Center [U01 HG004446]
- Collaborative Study on the Genetics of Alcoholism (COGA) [U10 AA008401]
- Collaborative Genetic Study of Nicotine Dependence (COGEND) [P01 CA089392]
- Family Study of Cocaine Dependence (FSCD) [R01 DA013423, R01 DA019963]
- NIH [AA07535, AA07728, AA13320, AA13321, AA14041, AA11998, AA17688, DA012854, DA019951, R01MH085542, R01MH093725, P50MH066392, P50MH080405, R01MH097276, RO1-MH-075916, P50M096891, P50MH084053S1, R37MH057881, R37MH057881S1, HHSN271201300031C, AG02219, AG05138, MH06692]
- Australian National Health and Medical Research Council [241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498]
- Australian Research Council [A7960034, A79906588, A79801419, DP0770096, DP0212016, DP0343921]
- FP-5 GenomEUtwin Project [QLG2-CT-2002-01254]
- National Institutes of Health (NIH) [RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535]
- Veterans Affairs Connecticut Healthcare Center
- Philadelphia Veterans Affairs Mental Illness Research, Education and Clinical Center
- Duke University
- Common Fund of the Office of the Director of the National Institutes of Health
- NCI
- NHGRI
- NHLBI
- NIDA
- NIMH
- NINDS
- NCI\SAIC-Frederick, Inc. (SAIC-F) subcontracts [10XS170, 10XS171, X10S172]
- Takeda Pharmaceuticals Company Limited
- F Hoffman-La Roche Ltd
- Division of Aging Biology, NIA
- Division of Geriatrics and Clinical Gerontology, NIA
- Intramural Research Program, NIA
- [K01DA037914]
- [R01DA036583]
- [AA011998_5978]
- [HHSN268201000029C]
- [DA006227]
- [DA033684]
- [N01MH000028]
- [MH090941]
- [MH101814]
- [MH090951]
- [MH090937]
- [MH101820]
- [MH101825]
- [MH090936]
- [MH101819]
- [MH090948]
- [MH101782]
- [MH101810]
- [MH101822]
- [Z01 AG000949-02]
- [Z01 AG000015-49]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [R01HD083614] Funding Source: NIH RePORTER
- NATIONAL CANCER INSTITUTE [U01CA200060, P01CA089392, P30CA091842] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000448, UL1TR002345] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR024992] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [U01HG004422, U01HG004446, R01HG007354, U01HG004438, U01HG009391, N01HG065403, R01HG007175] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES024992, U24ES026699] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008151] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH090948, R01MH090936, R01MH101822, R01MH090937, R01MH090951, R01MH093725, R01MH101814, R01MH097276, R37MH057881, R01MH080405, R01MH101825, R01MH057881, R01MH101584, R01MH075916, P50MH066392, R01MH101810, P50MH084053, P50MH096891, R01MH101782, R01MH085542, R01MH101820, R01MH090941, R01MH101819] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [Z01AG000015, R01AG045231, R01AG049789, U01AG052564, Z01AG000949, P50AG005138, P01AG002219] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [P50AA011998, R01AA011330, K05AA017688, R01AA017535, R01AA013321, P60AA011998, R01AA013320, R01AA007728, R01AA007535, R01AA014041, U10AA008401, R37AA007728] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [K02DA032573, R01DA023668, R56DA012854, R01DA017305, R01DA013423, K01DA037914, R01DA033369, R01DA019963, R01DA012849, RC2DA028909, R01DA018432, R01DA006227, R25DA027995, R01DA012690, R01DA036583, K08DA019951, R01DA012854, R01DA033684] Funding Source: NIH RePORTER
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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