Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications.
Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications.
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DOI：
10.1038/s41588-023-01563-z
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发表时间：
2023-12
期刊：
影响因子：
30.8
通讯作者：
Gelernter, Joel
中科院分区：
文献类型：
--
作者：
Levey, Daniel F.;Galimberti, Marco;Deak, Joseph D.;Wendt, Frank R.;Bhattacharya, Arjun;Koller, Dora;Harrington, Kelly M.;Quaden, Rachel;Johnson, Emma C.;Gupta, Priya;Biradar, Mahantesh;Lam, Max;Cooke, Megan;Rajagopal, Veera M.;Empke, Stefany L. L.;Zhou, Hang;Nunez, Yaira Z.;Kranzler, Henry R.;Edenberg, Howard J.;Agrawal, Arpana;Smoller, Jordan W.;Lencz, Todd;Hougaard, David M.;Borglum, Anders D.;Demontis, Ditte;Gaziano, J. Michael;Gandal, Michael J.;Polimanti, Renato;Stein, Murray B.;Gelernter, Joel
随着娱乐性使用大麻在许多地方被非刑事化，医疗用途被广泛认可，人们越来越担心大麻使用障碍（CanUD）的增加，这与许多医疗合并症有关。在这里，我们在百万退伍军人计划（MVP）中进行了CanUD的全基因组关联研究，随后对1，054，365名个体进行了荟萃分析。（ncases = 64，314）来自用于分配的参考组指定的四个广泛祖先（欧洲人n = 886，025，非洲人n = 123，208，美国混血儿n = 38，289，东亚人n = 6，843）。应用群体特异性方法计算每个祖先内基于单核苷酸多态性的遗传力。除最小人群（东亚）外，在所有人群中均观察到CanUD基于单核苷酸多态性的遗传力具有统计学显著性。我们发现了每个祖先独有的全基因组显著位点：欧洲人22个，非洲和东亚各2个，混合美洲血统1个。一项基于遗传信息的因果关系分析表明，CanUD的遗传易感性可能对肺癌风险产生影响，这表明未来可能出现不可预见的医疗和精神公共卫生后果，需要进一步研究，以将其与其他已知的风险因素（如吸烟）分开。多祖先全基因组关联荟萃分析确定大麻使用障碍的风险位点基因组结构方程模型和遗传相关性分析显示，与其他几个特征，包括冲动和精神病理学重叠。
As recreational use of cannabis is being decriminalized in many places and medical use widely sanctioned, there are growing concerns about increases in cannabis use disorder (CanUD), which is associated with numerous medical comorbidities. Here we performed a genome-wide association study of CanUD in the Million Veteran Program (MVP), followed by meta-analysis in 1,054,365 individuals (ncases = 64,314) from four broad ancestries designated by the reference panel used for assignment (European n = 886,025, African n = 123,208, admixed American n = 38,289 and East Asian n = 6,843). Population-specific methods were applied to calculate single nucleotide polymorphism-based heritability within each ancestry. Statistically significant single nucleotide polymorphism-based heritability for CanUD was observed in all but the smallest population (East Asian). We discovered genome-wide significant loci unique to each ancestry: 22 in European, 2 each in African and East Asian, and 1 in admixed American ancestries. A genetically informed causal relationship analysis indicated a possible effect of genetic liability for CanUD on lung cancer risk, suggesting potential unanticipated future medical and psychiatric public health consequences that require further study to disentangle from other known risk factors such as cigarette smoking. Multi-ancestry genome-wide association meta-analyses identify risk loci for cannabis use disorder. Genomic structural equation modeling and genetic correlation analyses show overlap with several other traits, including impulsivity and psychopathology.
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影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
3.9
作者：
Iglesias, Adriana I.;van der Lee, Sven J.;van Duijn, Cornelia M.
通讯作者：
van Duijn, Cornelia M.
自闭症谱系障碍（ASD）、精神分裂症和双相情感障碍中全转录组异构体水平失调
影响因子：
56.9
作者：
Gandal, Michael J.;Zhang, Pan;Geschwind, Daniel H.
通讯作者：
Geschwind, Daniel H.
影响因子：
3.4
作者：
Agrawal, Arpana;Lynskey, Michael T.;Bierut, Laura J.
通讯作者：
Bierut, Laura J.