美国加州大学圣迭戈分校Caroline M. Nievergelt等研究人员发现，全基因组关联分析确定95个风险基因位点，并为创伤后应激障碍的神经生物学提供见解。相关论文于2024年4月18日在线发表在《自然—遗传学》杂志上。

研究人员对1222882名欧洲血统的个体（137136例）和58051名非洲和美洲原住民血统的混血个体（13624例）进行了全基因组关联研究的多血统荟萃分析。研究人员确定了95个全基因组重要位点（80个新位点）。融合多组学方法确定了43个潜在的致病基因，大致分为神经递质和离子通道突触调节因子（如GRIA1、GRM8和CACNA1E）、发育、轴突导向和转录因子（如FOXP2、EFNA5和DCC）、突触结构和功能基因（如PCLO、NCAM1和PDE4B）以及内分泌或免疫调节剂（如ESR1、TRAF3和TANK）。

其他前列基因还影响着压力、免疫、恐惧和威胁相关过程，这些过程以前曾被假设为创伤后应激障碍（PTSD）神经生物学的基础。这些发现加强了人们对PTSD病理生理学相关神经生物学系统的了解，同时也开辟了新的研究领域。

研究人员表示，与大多数其他精神疾病相比，PTSD遗传学的特点是可发现性较低。因此，以往的遗传学研究对生物学认识的贡献有限。

附：英文原文

Title: Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder

Author: Nievergelt, Caroline M., Maihofer, Adam X., Atkinson, Elizabeth G., Chen, Chia-Yen, Choi, Karmel W., Coleman, Jonathan R. I., Daskalakis, Nikolaos P., Duncan, Laramie E., Polimanti, Renato, Aaronson, Cindy, Amstadter, Ananda B., Andersen, Soren B., Andreassen, Ole A., Arbisi, Paul A., Ashley-Koch, Allison E., Austin, S. Bryn, Avdibegovi, Esmina, Babi, Dragan, Bacanu, Silviu-Alin, Baker, Dewleen G., Batzler, Anthony, Beckham, Jean C., Belangero, Sintia, Benjet, Corina, Bergner, Carisa, Bierer, Linda M., Biernacka, Joanna M., Bierut, Laura J., Bisson, Jonathan I., Boks, Marco P., Bolger, Elizabeth A., Brandolino, Amber, Breen, Gerome, Bressan, Rodrigo Affonseca, Bryant, Richard A., Bustamante, Angela C., Bybjerg-Grauholm, Jonas, Bkvad-Hansen, Marie, Brglum, Anders D., Brte, Sigrid, Cahn, Leah, Calabrese, Joseph R., Caldas-de-Almeida, Jose Miguel, Chatzinakos, Chris, Cheema, Sheraz, Clouston, Sean A. P., Colodro-Conde, Luca, Coombes, Brandon J., Cruz-Fuentes, Carlos S., Dale, Anders M., Dalvie, Shareefa, Davis, Lea K., Deckert, Jrgen, Delahanty, Douglas L., Dennis, Michelle F., Desarnaud, Frank, DiPietro, Christopher P., Disner, Seth G.

Issue&Volume: 2024-04-18

Abstract: Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

DOI: 10.1038/s41588-024-01707-9

Source: https://www.nature.com/articles/s41588-024-01707-9