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<p>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 (<i>P</i> &lt; 2.38 × 10<sup>−9</sup>), 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.</p>

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Cross-ancestry and sex-stratified genome-wide association analyses of amygdala and subnucleus volumes

  • 期刊论文

  • 发表日期：

    2025年3月17日

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  • Yuan Ji,
  • Nana Liu,
  • Yunjun Yang,
  • Meiyun Wang,
  • Jingliang Cheng,
  • Wenzhen Zhu,
  • Shijun Qiu,
  • Zuojun Geng,
  • Guangbin Cui,
  • Yongqiang Yu,
  • Weihua Liao,
  • Hui Zhang,
  • Bo Gao,
  • Xiaojun Xu,
  • Tong Han,
  • Zhenwei Yao,
  • Quan Zhang,
  • Wen Qin,
  • Feng Liu,
  • Meng Liang,
  • Sijia Wang,
  • Qiang Xu,
  • Jiayuan Xu,
  • Jilian Fu,
  • Peng Zhang,
  • Wei Li,
  • Dapeng Shi,
  • Caihong Wang,
  • Su Lui,
  • Zhihan Yan,
  • Feng Chen,
  • Jing Zhang,
  • Wen Shen,
  • Yanwei Miao,
  • Dawei Wang,
  • Jia-Hong Gao,
  • Xiaochu Zhang,
  • Kai Xu,
  • Xi-Nian Zuo,
  • Longjiang Zhang,
  • Zhaoxiang Ye,
  • Mulin Jun Li,
  • Junfang Xian,
  • Bing Zhang,
  • Chunshui Yu

摘要

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 × 10−9), 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.