Genome-wide association studies of brain diffusion kurtosis imaging phenotypes
BACKGROUND: As an extension of diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI) quantifies non-Gaussian water diffusion and has been applied to explore brain disorders. However, the genetic architecture of brain DKI phenotypes remains unknown. METHODS: Here, we estimated heritability and conducted genome-wide association studies (GWASs) for 804 DKI phenotypes across 188 brain structures in 4183 participants. To determine whether DKI-GWASs provides genetic insights beyond DTI-GWASs, we compared results from 804 DKI-GWASs and 752 DTI-GWASs in the same cohort. To clarify the biological significance of DKI phenotypes, we examined associations between DKI phenotypes and brain health-related outcomes within the CHIMGEN, and explored associations between polygenic risk scores (PRSs) of DKI phenotypes and mental disorders in the UK Biobank. FINDINGS: ). INTERPRETATION: This study delineates the genetic architecture of brain DKI phenotypes, identifies complementary genetic insights into brain microstructure, and provides biologically relevant endophenotypes for investigating neural mechanisms underlying brain disorders. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program of China, Tianjin Key Medical Discipline Construction Project, and Tianjin Natural Science Foundation.
Authors
- Jiahui Lin
- Huaigui Liu (ORCID: https://orcid.org/0000-0003-3660-3770)
- Fangshi Zhao
- Qiang Xu (ORCID: https://orcid.org/0000-0003-4744-5616)
- Kaizhong Xue (ORCID: https://orcid.org/0000-0002-4255-8913)
- Wenshuang Zhu (ORCID: https://orcid.org/0000-0002-6327-7934)
- C YU
- Jiayang Yang
- Qingqing Diao (ORCID: https://orcid.org/0009-0002-7067-9998)
- M T Li
- Qian Su (ORCID: https://orcid.org/0000-0003-4351-2631)
- Lixue Xu (ORCID: https://orcid.org/0000-0002-7152-2741)
- Yongjie Xu (ORCID: https://orcid.org/0000-0001-8417-3168)
- Jiance Li
- L J Zhang (ORCID: https://orcid.org/0009-0009-5783-8385)
- Tianying Gao
- Xianting Sun
- Xiaochu Zhang (ORCID: https://orcid.org/0000-0002-7541-0130)
- Huanhuan Cai (ORCID: https://orcid.org/0000-0003-3426-8630)
- Ya Wen
- Yongqin Xiong (ORCID: https://orcid.org/0000-0002-2435-9064)
- Zhaoxiang Ye (ORCID: https://orcid.org/0000-0003-3157-8393)
- Xi Zhang (ORCID: https://orcid.org/0000-0002-4638-3997)
- Yan Zhang (ORCID: https://orcid.org/0000-0002-0704-7421)
- Nana Liu (ORCID: https://orcid.org/0000-0002-1075-5883)
- Jilian Fu
- Yanwei Miao (ORCID: https://orcid.org/0000-0003-3103-9824)
- Weihua Liao (ORCID: https://orcid.org/0000-0002-1926-3527)
- Nannan Pan (ORCID: https://orcid.org/0009-0008-7129-0275)
- Yi-Xiang Wang (ORCID: https://orcid.org/0000-0002-4021-4228)
- Xi-Nian Zuo
- Su Lui
- J Gao
- Dan Zhu (ORCID: https://orcid.org/0009-0005-0636-5988)
- Hui Xue
- Congcong Yuan
- Jiayuan Xu
- Junlin Shen
- Jie Sun
- Kai Xu
- Bing Zhang
- Wen Qin
- Sijia Wang
- Yongqiang Yu
- Dapeng Shi
- Jiajia Zhu
- Yingying Xie
- Wen Shen
- Jing Zhang
- Guangbin Cui
- Shijie Zhang
- Yuan Ji
- Zhimin Li
- Jie Tang
- Bingjie Wu
- Feng Chen
- Zhihan Yan
- Quan Zhang
- Peng Zhang
- Yujuan Cao
- Dawei Wang
- Meiyun Wang
- Feng Liu
- Zirui Wang
- Xi Guo
- Yanjun Li
- Xinjun Suo
- Zuojun Geng
- Bo Gao
- Lining Guo
- Meng Liang
- Hao Ding
- Hui Zhang
- Bingbing Yang
- Wenzhen Zhu
- Junpeng Liu
- Junfang Xian
- Yaodan Zhang
- Jingliang Cheng
- Xiaojun Xu
- Tong Han
- Shijun Qiu
- Caihong Wang
- Wei Li
- Zhenwei Yao
Institutions
- Hebei Medical University (CN)
- University of Science and Technology of China (CN)
- Beijing Tongren Hospital (CN)
- Central South University (CN)
- Guiyang Medical University (CN)
- Shanxi Medical University (CN)
- Xuzhou Medical College (CN)
- Capital Medical University (CN)
- Dalian Medical University (CN)
- Anhui Medical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking University (CN)
- Sichuan University (CN)
- Beijing Normal University (CN)
- Wenzhou Medical University (CN)
- Tianjin First Center Hospital (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- Tianjin Medical University General Hospital (CN)
- Tianjin Medical University Cancer Institute and Hospital (CN)
- Yuhuangding Hospital (CN)
- Chinese People's Armed Police Force Medical College Affiliated Hospital (CN)
- West China Hospital of Sichuan University (CN)
- Center for Excellence in Brain Science and Intelligence Technology (CN)
- Second Hospital of Hebei Medical University (CN)
- Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University (CN)
- Tianjin Huanhu Hospital (CN)
- First Affiliated Hospital of Guangzhou University of Chinese Medicine (CN)
- Nanjing Drum Tower Hospital (CN)
- Chinese Institute for Brain Research (CN)
- Lanzhou University Second Hospital (CN)
- First Hospital of Shanxi Medical University (CN)
- Hainan General Hospital (CN)
- Henan Provincial People's Hospital (CN)
- First Affiliated Hospital of Anhui Medical University (CN)
- Second Affiliated Hospital of Nanjing Medical University (CN)
- First Affiliated Hospital of Dalian Medical University (CN)
- Tang Du Hospital (CN)
- First Affiliated Hospital of Zhengzhou University (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- Huashan Hospital (CN)
- Xiangya Hospital Central South University (CN)
- Tongji Hospital (CN)
- Center for Life Sciences (CN)
- Qilu Hospital of Shandong University (CN)
- Huazhong University of Science and Technology (CN)
- Tianjin Medical University (CN)
- Lanzhou University (CN)
- Hainan Medical University (CN)
- Nanjing Medical University (CN)
- Nanjing University (CN)
Publication Details
- Journal
- EBioMedicine
- Published
- 2026-04-17
- DOI
- https://doi.org/10.1016/j.ebiom.2026.106261
- Primary Topic
- Advanced Neuroimaging Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Tianjin City
- National Key Research and Development Program of China