美国耶鲁大学Joel Gelernter等研究人员合作发现，大麻使用障碍多基因组全关联研究揭示疾病生物学和对公共卫生的影响。该研究于2023年11月20日在线发表于《自然—遗传学》杂志。

研究人员在“百万退伍军人计划”（Million Veteran Program，MVP）中对大麻使用障碍（CanUD）进行了全基因组关联研究，随后对来自用于分配的参考库所指定的四大血统（欧洲人n=886025、非洲人n=123208、混血美国人n=38289和东亚人n=6843）的1054365人（n_cases=64314）进行了荟萃分析。研究人员采用特定人群的方法计算每个血统中基于单核苷酸多态性的遗传率。除了最小的人群（东亚人）外，在所有人群中都观察到了基于单核苷酸多态性的具有统计学意义的CanUD遗传率。研究人员发现了每个血统特有的全基因组重要位点：欧洲血统22个，非洲和东亚血统各2个，混血美洲血统1个。遗传因果关系分析表明，CanUD的遗传责任可能会对肺癌风险产生影响，这表明未来可能会出现意想不到的医疗和精神公共卫生后果，需要进一步研究才能将其与吸烟等其他已知风险因素区分开来。

据悉，随着许多地方将娱乐性使用大麻非刑罪化并广泛认可医疗使用大麻，人们越来越担心CanUD的增加，这与许多医疗合并症有关。

附：英文原文

Title: Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications

Author: 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., Brglum, Anders D., Demontis, Ditte, Gaziano, J. Michael, Gandal, Michael J., Polimanti, Renato, Stein, Murray B., Gelernter, Joel

Issue&Volume: 2023-11-20

Abstract: 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.

DOI: 10.1038/s41588-023-01563-z

Source: https://www.nature.com/articles/s41588-023-01563-z