美国耶鲁大学Joel Gelernter团队经过不懈努力取得一项新成果。他们通过对435,563名问题饮酒个体进行全基因组荟萃分析，揭示了其生物学以及与其他特征的关系。该项研究成果发表在2020年5月25日的《自然—神经科学》上。

研究人员对435,563名有欧洲血统的个体进行了酗酒（PAU）表型荟萃分析，并结合了饮酒障碍和酗酒。研究人员确定了29种独立的风险变体，其中19种是新发现的。PAU与138种表型具有遗传相关性，包括食物使用和精神状态。

在独立生物库样本（BioVU，n = 67,589）中进行的全基因组多基因风险评分分析证实了PAU与食物使用和精神疾病之间的遗传相关性。PAU的遗传力在大脑以及保守和调控基因组区域富集。孟德尔随机取样表明药物使用、精神状态、冒险行为和认知表现与PAU之间具有因果关系。总之，这项大型PAU荟萃分析确定了新的风险基因座，并揭示了与其他性状的遗传关系。

据介绍，在世界范围内，酗酒是造成死亡和残疾的主要原因之一。尽管全基因组关联分析已经确定了PAU的风险基因，但尚未完全了解此性状的遗传结构。

附：英文原文

Title: Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits

Author: Hang Zhou, Julia M. Sealock, Sandra Sanchez-Roige, Toni-Kim Clarke, Daniel F. Levey, Zhongshan Cheng, Boyang Li, Renato Polimanti, Rachel L. Kember, Rachel Vickers Smith, Johan H. Thygesen, Marsha Y. Morgan, Stephen R. Atkinson, Mark R. Thursz, Mette Nyegaard, Manuel Mattheisen, Anders D. Brglum, Emma C. Johnson, Amy C. Justice, Abraham A. Palmer, Andrew McQuillin, Lea K. Davis, Howard J. Edenberg, Arpana Agrawal, Henry R. Kranzler, Joel Gelernter

Issue&Volume: 2020-05-25

Abstract: Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. Although genome-wide association studies have identified PAU risk genes, the genetic architecture of this trait is not fully understood. We conducted a proxy-phenotype meta-analysis of PAU, combining alcohol use disorder and problematic drinking, in 435,563European-ancestry individuals. We identified 29independent risk variants, 19 of them novel. PAU was genetically correlated with 138phenotypes, including substance use and psychiatric traits. Phenome-wide polygenic risk score analysis in an independent biobank sample (BioVU, n=67,589) confirmed the genetic correlations between PAU and substance use and psychiatric disorders. Genetic heritability of PAU was enriched in brain and in conserved and regulatory genomic regions. Mendelian randomization suggested causal effects on liability to PAU of substance use, psychiatric status, risk-taking behavior and cognitive performance. In summary, this large PAU meta-analysis identified novel risk loci and revealed genetic relationships with numerous other traits.

DOI: 10.1038/s41593-020-0643-5

Source: https://www.nature.com/articles/s41593-020-0643-5