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

Yuan Ji^#¹, Nana Liu^#¹, Yunjun Yang^#², Meiyun Wang^{3

4}, Jingliang Cheng⁵, Wenzhen Zhu⁶, Shijun Qiu⁷, Zuojun Geng⁸, Guangbin Cui⁹, Yongqiang Yu¹⁰, Weihua Liao^{11

12

13}, Hui Zhang¹⁴, Bo Gao^{15

16}, Xiaojun Xu¹⁷, Tong Han¹⁸, Zhenwei Yao¹⁹, Quan Zhang²⁰, Wen Qin¹, Feng Liu¹, Meng Liang²¹, Sijia Wang¹, Qiang Xu¹, Jiayuan Xu¹, Jilian Fu¹, Peng Zhang²², Wei Li²², Dapeng Shi³, Caihong Wang⁵, Su Lui^{23

24}, Zhihan Yan²⁵, Feng Chen²⁶, Jing Zhang^{27

28}, Wen Shen²⁹, Yanwei Miao³⁰, Dawei Wang³¹, Jia-Hong Gao³², Xiaochu Zhang³³, Kai Xu³⁴, Xi-Nian Zuo^{35

36}, Longjiang Zhang³⁷, Zhaoxiang Ye²², Mulin Jun Li³⁸, Junfang Xian³⁹, Bing Zhang⁴⁰, Chunshui Yu^{41

42}; CHIMGEN Consortium

Affiliations

¹ Department of Radiology, Tianjin Key Laboratory of Functional Imaging and State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital, Tianjin, China.
² Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³ Department of Radiology, Henan Provincial People's Hospital & Zhengzhou University People's Hospital, Zhengzhou, China.
⁴ Biomedical Institute, Henan Academy of Sciences, Zhengzhou, China.
⁵ Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁶ Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁷ Department of Medical Imaging, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
⁸ Department of Medical Imaging, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
⁹ Functional and Molecular Imaging Key Lab of Shaanxi Province & Department of Radiology, Tangdu Hospital, Air Force Medical University, Xi'an, China.
¹⁰ Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
¹¹ Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.
¹² Molecular Imaging Research Center of Central South University, Changsha, China.
¹³ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
¹⁴ Department of Radiology, The First Hospital of Shanxi Medical University, Taiyuan, China.
¹⁵ Department of Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
¹⁶ Department of Radiology, Yantai Yuhuangding Hospital, Yantai, China.
¹⁷ Department of Radiology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
¹⁸ Department of Radiology, Tianjin Huanhu Hospital, Tianjin, China.
¹⁹ Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China.
²⁰ Department of Radiology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, China.
²¹ School of Medical Imaging and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University, Tianjin, China.
²² Department of Radiology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
²³ Department of Radiology, Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, China.
²⁴ Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China.
²⁵ Department of Radiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
²⁶ Department of Radiology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China.
²⁷ Department of Magnetic Resonance, Lanzhou University Second Hospital, Lanzhou, China.
²⁸ Gansu Province Clinical Research Center for Functional and Molecular Imaging, Lanzhou, China.
²⁹ Department of Radiology, Tianjin First Center Hospital, Tianjin, China.
³⁰ Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
³¹ Department of Radiology, Qilu Hospital of Shandong University, Jinan, China.
³² Center for MRI Research, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
³³ Division of Life Science and Medicine, University of Science & Technology of China, Hefei, China.
³⁴ Department of Radiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
³⁵ Developmental Population Neuroscience Research Center at IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
³⁶ Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
³⁷ Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
³⁸ Department of Bioinformatics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
³⁹ Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China. cjr.xianjunfang@vip.163.com.
⁴⁰ Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. zhangbing_nanjing@vip.163.com.
⁴¹ Department of Radiology, Tianjin Key Laboratory of Functional Imaging and State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital, Tianjin, China. chunshuiyu@tmu.edu.cn.
⁴² School of Medical Imaging and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University, Tianjin, China. chunshuiyu@tmu.edu.cn.

^# Contributed equally.

PMID: 40097784
DOI: 10.1038/s41588-025-02136-y

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

Yuan Ji et al. Nat Genet. 2025 Apr.

. 2025 Apr;57(4):839-850.

doi: 10.1038/s41588-025-02136-y. Epub 2025 Mar 17.

Authors

Affiliations

¹ Department of Radiology, Tianjin Key Laboratory of Functional Imaging and State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital, Tianjin, China.
² Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³ Department of Radiology, Henan Provincial People's Hospital & Zhengzhou University People's Hospital, Zhengzhou, China.
⁴ Biomedical Institute, Henan Academy of Sciences, Zhengzhou, China.
⁵ Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁶ Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁷ Department of Medical Imaging, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
⁸ Department of Medical Imaging, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
⁹ Functional and Molecular Imaging Key Lab of Shaanxi Province & Department of Radiology, Tangdu Hospital, Air Force Medical University, Xi'an, China.
¹⁰ Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
¹¹ Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.
¹² Molecular Imaging Research Center of Central South University, Changsha, China.
¹³ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
¹⁴ Department of Radiology, The First Hospital of Shanxi Medical University, Taiyuan, China.
¹⁵ Department of Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
¹⁶ Department of Radiology, Yantai Yuhuangding Hospital, Yantai, China.
¹⁷ Department of Radiology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
¹⁸ Department of Radiology, Tianjin Huanhu Hospital, Tianjin, China.
¹⁹ Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China.
²⁰ Department of Radiology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, China.
²¹ School of Medical Imaging and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University, Tianjin, China.
²² Department of Radiology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
²³ Department of Radiology, Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, China.
²⁴ Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China.
²⁵ Department of Radiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
²⁶ Department of Radiology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China.
²⁷ Department of Magnetic Resonance, Lanzhou University Second Hospital, Lanzhou, China.
²⁸ Gansu Province Clinical Research Center for Functional and Molecular Imaging, Lanzhou, China.
²⁹ Department of Radiology, Tianjin First Center Hospital, Tianjin, China.
³⁰ Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
³¹ Department of Radiology, Qilu Hospital of Shandong University, Jinan, China.
³² Center for MRI Research, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
³³ Division of Life Science and Medicine, University of Science & Technology of China, Hefei, China.
³⁴ Department of Radiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
³⁵ Developmental Population Neuroscience Research Center at IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
³⁶ Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
³⁷ Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
³⁸ Department of Bioinformatics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
³⁹ Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China. cjr.xianjunfang@vip.163.com.
⁴⁰ Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. zhangbing_nanjing@vip.163.com.
⁴¹ Department of Radiology, Tianjin Key Laboratory of Functional Imaging and State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital, Tianjin, China. chunshuiyu@tmu.edu.cn.
⁴² School of Medical Imaging and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University, Tianjin, China. chunshuiyu@tmu.edu.cn.

^# Contributed equally.

PMID: 40097784
DOI: 10.1038/s41588-025-02136-y

Abstract

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.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

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