Pasman Joëlle A, Verweij Karin J H, Gerring Zachary, Stringer Sven, Sanchez-Roige Sandra, Treur Jorien L, Abdellaoui Abdel, Nivard Michel G, Baselmans Bart M L, Ong Jue-Sheng, Ip Hill F, van der Zee Matthijs D, Bartels Meike, Day Felix R, Fontanillas Pierre, Elson Sarah L, de Wit Harriet, Davis Lea K, MacKillop James, Derringer Jaime L, Branje Susan J T, Hartman Catharina A, Heath Andrew C, van Lier Pol A C, Madden Pamela A F, Mägi Reedik, Meeus Wim, Montgomery Grant W, Oldehinkel A J, Pausova Zdenka, Ramos-Quiroga Josep A, Paus Tomas, Ribases Marta, Kaprio Jaakko, Boks Marco P M, Bell Jordana T, Spector Tim D, Gelernter Joel, Boomsma Dorret I, Martin Nicholas G, MacGregor Stuart, Perry John R B, Palmer Abraham A, Posthuma Danielle, Munafò Marcus R, Gillespie Nathan A, Derks Eske M, Vink Jacqueline M
Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands.
Amsterdam UMC, University of Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands.
Nat Neurosci. 2018 Sep;21(9):1161-1170. doi: 10.1038/s41593-018-0206-1. Epub 2018 Aug 27.
Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.
大麻使用是一种可遗传的特质，与不良心理健康结果相关。在迄今为止针对终生大麻使用的最大规模全基因组关联研究（GWAS，N = 184,765）中，我们在六个区域鉴定出八个全基因组显著的独立单核苷酸多态性。所有测量的遗传变异综合起来解释了11%的方差。基于基因的测试在16个区域揭示了35个显著基因，S-PrediXcan分析表明，与非大麻使用者相比，21个基因在大麻使用者中有不同的表达水平。不同分析中最显著的发现是CADM2，它与物质使用和冒险行为有关。在25个测试的物质使用和心理健康相关特质中，有14个发现了显著的遗传相关性，包括吸烟、饮酒、精神分裂症和冒险行为。孟德尔随机化分析显示有证据表明精神分裂症风险对大麻使用有因果正向影响。总体而言，我们的研究为大麻使用的病因及其与心理健康的关系提供了新的见解。
