Sun Yaoyao, Zhao Guorui, Zhang Yuyanan, Lu Zhe, Kang Zhewei, Sun Junyuan, Feng Xiaoyang, Guo Jing, Liao Yundan, Guo Liangkun, Yang Yang, Zhang Dai, Bi Wenjian, Chen Runsen, Yue Weihua
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China.
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China; Chinese Institute for Brain Research, Beijing 102206, China.
Cell Rep Med. 2025 May 20;6(5):102119. doi: 10.1016/j.xcrm.2025.102119. Epub 2025 May 9.
Non-suicidal self-injury (NSSI) is highly prevalent in recent years, but the genetic architecture remains unknown. We perform a multitrait analysis of genome-wide association study on NSSI, incorporating self-harm and suicide attempt. Common genetic variants account for 6.03% of NSSI variance. Three risk loci are associated with NSSI at 7q31.2 (rs62474683), DCC (rs4372758), and LCA5L/GET1/GET1-SH3BGR (rs2837022). Increased expression levels of GET1/SH3BGR in hippocampus relates to NSSI risk. Fine-mapping identifies seven likely causal variants, and colocalization with rs4281987 and rs2837022 evidences SH3BGR/GET1 expression in hippocampus to NSSI. In an independent sample, polygenic risk score for NSSI is associated with children's NSSI behavior, suicidal ideation, and suicide attempt (odds ratios [ORs]: 1.14-1.37). Reduction in right temporal pole volume mediates NSSI genetic liability for children's NSSI behavior. Walking for pleasure and exercises like swimming and bowling reduces NSSI risk, whereas smoking increases it. This study elucidates the NSSI genetic basis and its impact on children's emotions, behavior, and brain structure.
近年来，非自杀性自伤行为（NSSI）极为普遍，但其遗传结构仍不明晰。我们对NSSI进行了全基因组关联研究的多性状分析，纳入了自我伤害和自杀未遂情况。常见遗传变异占NSSI变异的6.03%。三个风险位点与NSSI相关，分别位于7q31.2（rs62474683）、DCC（rs4372758）以及LCA5L/GET1/GET1 - SH3BGR（rs2837022）。海马体中GET1/SH3BGR表达水平升高与NSSI风险相关。精细定位确定了七个可能的因果变异，与rs4281987和rs2837022的共定位证明了海马体中SH3BGR/GET1表达与NSSI的关联。在一个独立样本中，NSSI的多基因风险评分与儿童的NSSI行为、自杀意念和自杀未遂相关（优势比[OR]：1.14 - 1.37）。右侧颞极体积减小介导了儿童NSSI行为的NSSI遗传易感性。为了愉悦而散步以及游泳和保龄球等运动可降低NSSI风险，而吸烟则会增加风险。本研究阐明了NSSI的遗传基础及其对儿童情绪、行为和脑结构的影响。
