美国耶鲁大学医学院Renato Polimanti团队近期取得重要工作进展，他们从大规模多血统全基因组关联研究中发现了焦虑症相关基因，并深入了解其生物学特征。相关研究成果2024年9月18日在线发表于《自然—遗传学》杂志上。

研究人员利用来自120多万参与者的信息，包括97383个病例，调查了五个大陆群体的焦虑症遗传学。通过祖先特异性和跨祖先全基因组关联研究，研究人员确定了51个与焦虑相关的位点，其中39个是新的。此外，来自欧洲血统个体的多基因风险评分与非洲、美国和东亚混合群体的焦虑有关。

边缘系统、大脑皮层、小脑、中脑、内嗅皮层和脑干中表达的基因增强了焦虑的遗传性。全转录组和全蛋白质组分析突出了115个通过脑特异性和跨组织调节与焦虑相关的基因。焦虑还显示出与抑郁症、精神分裂症和双相情感障碍的整体和局部遗传相关性，以及与几个身体健康领域的广泛多效性。

总之，这一研究扩展了人们对焦虑症遗传风险和发病机制的认识，强调了调查不同人群和整合多组学信息的重要性。

附：英文原文

Title: Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study

Author: Friligkou, Eleni, Lkhammer, Solveig, Cabrera-Mendoza, Brenda, Shen, Jie, He, Jun, Deiana, Giovanni, Zanoaga, Mihaela Diana, Asgel, Zeynep, Pilcher, Abigail, Di Lascio, Luciana, Makharashvili, Ana, Koller, Dora, Tylee, Daniel S., Pathak, Gita A., Polimanti, Renato

Issue&Volume: 2024-09-18

Abstract: We leveraged information from more than 1.2 million participants, including 97,383 cases, to investigate the genetics of anxiety disorders across five continental groups. Through ancestry-specific and cross-ancestry genome-wide association studies, we identified 51 anxiety-associated loci, 39 of which were novel. In addition, polygenic risk scores derived from individuals of European descent were associated with anxiety in African, admixed American and East Asian groups. The heritability of anxiety was enriched for genes expressed in the limbic system, cerebral cortex, cerebellum, metencephalon, entorhinal cortex and brain stem. Transcriptome-wide and proteome-wide analyses highlighted 115 genes associated with anxiety through brain-specific and cross-tissue regulation. Anxiety also showed global and local genetic correlations with depression, schizophrenia and bipolar disorder and widespread pleiotropy with several physical health domains. Overall, this study expands our knowledge regarding the genetic risk and pathogenesis of anxiety disorders, highlighting the importance of investigating diverse populations and integrating multi-omics information.

DOI: 10.1038/s41588-024-01908-2

Source: https://www.nature.com/articles/s41588-024-01908-2