杏仁核及亚核体积的跨血统和性别分层全基因组关联分析。
Cross-ancestry and sex-stratified genome-wide association analyses of amygdala and subnucleus volumes.
作者信息
Ji Yuan, Liu Nana, Yang Yunjun, Wang Meiyun, Cheng Jingliang, Zhu Wenzhen, Qiu Shijun, Geng Zuojun, Cui Guangbin, Yu Yongqiang, Liao Weihua, Zhang Hui, Gao Bo, Xu Xiaojun, Han Tong, Yao Zhenwei, Zhang Quan, Qin Wen, Liu Feng, Liang Meng, Wang Sijia, Xu Qiang, Xu Jiayuan, Fu Jilian, Zhang Peng, Li Wei, Shi Dapeng, Wang Caihong, Lui Su, Yan Zhihan, Chen Feng, Zhang Jing, Shen Wen, Miao Yanwei, Wang Dawei, Gao Jia-Hong, Zhang Xiaochu, Xu Kai, Zuo Xi-Nian, Zhang Longjiang, Ye Zhaoxiang, Li Mulin Jun, Xian Junfang, Zhang Bing, Yu Chunshui
机构信息
Department of Radiology, Tianjin Key Laboratory of Functional Imaging and State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital, Tianjin, China.
Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
出版信息
Nat Genet. 2025 Apr;57(4):839-850. doi: 10.1038/s41588-025-02136-y. Epub 2025 Mar 17.
The amygdala is a small but critical multi-nucleus structure for emotion, cognition and neuropsychiatric disorders. Although genetic associations with amygdala volumetric traits have been investigated in sex-combined European populations, cross-ancestry and sex-stratified analyses are lacking. Here we conducted cross-ancestry and sex-stratified genome-wide association analyses for 21 amygdala volumetric traits in 6,923 Chinese and 48,634 European individuals. We identified 191 variant-trait associations (P < 2.38 × 10), including 47 new associations (12 new loci) in sex-combined univariate analyses and seven additional new loci in sex-combined and sex-stratified multivariate analyses. We identified 12 ancestry-specific and two sex-specific associations. The identified genetic variants include 16 fine-mapped causal variants and regulate amygdala and fetal brain gene expression. The variants were enriched for brain development and colocalized with mood, cognition and neuropsychiatric disorders. These results indicate that cross-ancestry and sex-stratified genetic association analyses may provide insight into the genetic architectures of amygdala and subnucleus volumes.
杏仁核是一个对于情绪、认知和神经精神疾病而言虽小却至关重要的多核结构。尽管在欧洲人群合并性别样本中已对杏仁核体积特征的遗传关联进行了研究，但跨血统和按性别分层的分析仍较为缺乏。在此，我们对6923名中国人和48634名欧洲人的21种杏仁核体积特征进行了跨血统和按性别分层的全基因组关联分析。我们鉴定出了191个变异 - 性状关联（P < 2.38×10），包括在合并性别单变量分析中的47个新关联（12个新位点）以及在合并性别和按性别分层的多变量分析中的另外7个新位点。我们鉴定出了12个特定血统关联和2个性别特异性关联。所鉴定出的遗传变异包括16个精细定位的因果变异，并调控杏仁核和胎儿大脑基因表达。这些变异在大脑发育方面显著富集，并与情绪、认知和神经精神疾病共定位。这些结果表明，跨血统和按性别分层的遗传关联分析可能为杏仁核及亚核体积的遗传结构提供见解。
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