| Title: | Genome-wide association studies of brain diffusion kurtosis imaging phenotypes |
| Journal: | EBioMedicine |
| Published: | 17 Apr 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42000319/ |
| DOI: | https://doi.org/10.1016/j.ebiom.2026.106261 |
Publication 17953
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Abstract
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.</p>
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.</p>
FINDINGS: Of 804 DKI phenotypes, 275 showed significant heritability (P < 0.05; h2 range: 0.143-0.602). We detected 280 significant associations (P < 5 × 10-8), with 38 surviving Bonferroni correction (P < 1.54 × 10-10). These associations were unevenly distributed across chromosomes, DKI phenotype subgroups, and brain structures. Among 229 independent variant-structure associations for DKI, 175 (76.4%) were DKI-specific. We observed 930 associations between DKI phenotypes and brain health-related outcomes (P < 0.05; ten Bonferroni-significant with P < 1.02 × 10-5), and 200 between PRSs and mental disorders (P < 0.05; one Bonferroni-significant with P < 9.61 × 10-5).</p>
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.</p>
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.</p>
213 Authors
- Jilian Fu
- Jianhua Wang
- Hui Xue
- Meiyun Wang
- Bing Zhang
- Wenzhen Zhu
- Shijun Qiu
- Zuojun Geng
- Guangbin Cui
- Quan Zhang
- Yongqiang Yu
- Weihua Liao
- Bo Gao
- Xiaojun Xu
- Tong Han
- Zhenwei Yao
- Mulin Jun Li
- Feng Liu
- Meng Liang
- Sijia Wang
- Qiang Xu
- Jiayuan Xu
- Peng Zhang
- Wei Li
- Dapeng Shi
- Caihong Wang
- Su Lui
- Zhihan Yan
- Feng Chen
- Jing Zhang
- Jiance Li
- Wen Shen
- Yanwei Miao
- Dawei Wang
- Junfang Xian
- Jia-Hong Gao
- Xiaochu Zhang
- Kai Xu
- Xi-Nian Zuo
- Longjiang Zhang
- Zhaoxiang Ye
- Jingliang Cheng
- Wen Qin
- Hui Zhang
- Chunshui Yu
- Chunshui Yu
- Quan Zhang
- Wen Qin
- Feng Liu
- Junping Wang
- Qiang Xu
- Jiayuan Xu
- Xue Zhang
- Xinjun Suo
- Jilian Fu
- Congcong Yuan
- Yuan Ji
- Hui Xue
- Tianying Gao
- Junpeng Liu
- Yanjun Li
- Xi Guo
- Lixue Xu
- Jiajia Zhu
- Huaigui Liu
- Fangshi Zhao
- Jie Sun
- Yongjie Xu
- Huanhuan Cai
- Jie Tang
- Yaodan Zhang
- Yongqin Xiong
- Xianting Sun
- Nannan Pan
- Xue Zhang
- Jiayang Yang
- Nana Liu
- Ya Wen
- Dan Zhu
- Bingjie Wu
- Wenshuang Zhu
- Qingqing Diao
- Yujuan Cao
- Bingbing Yang
- Lining Guo
- Yingying Xie
- Jiahui Lin
- Zhimin Li
- Yan Zhang
- Kaizhong Xue
- Zirui Wang
- Junlin Shen
- Meng Liang
- Xuejun Zhang
- Hao Ding
- Qian Su
- Sijia Wang
- Mulin Jun Li
- Shijie Zhang
- Jianhua Wang
- Zhaoxiang Ye
- Peng Zhang
- Wei Li
- Meiyun Wang
- Dapeng Shi
- Lun Ma
- Yan Bai
- Min Guan
- Wei Wei
- Jingliang Cheng
- Caihong Wang
- Peifang Miao
- Fuhong Duan
- Yafei Guo
- Weijian Wang
- Longjiang Zhang
- Lijuan Zheng
- Li Lin
- Yunfei Wang
- Han Zhang
- Xinyuan Zhang
- Bing Zhang
- Zhao Qing
- Sichu Wu
- Junxia Wang
- Yi Sun
- Yang He
- Xi-Nian Zuo
- Zhe Zhang
- Yin-Shan Wang
- Quan Zhou
- Wenzhen Zhu
- Tian Tian
- Shijun Qiu
- Yi Liang
- Yujie Liu
- Hui Zeng
- Jingxian Chen
- Kai Xu
- Haitao Ge
- Peng Xu
- Cailuan Lu
- Chen Wu
- Xiaoying Yang
- Zuojun Geng
- Yuzhao Wang
- Yankai Wu
- Xuran Feng
- Ling Li
- Duo Gao
- Xiaochu Zhang
- Rujing Zha
- Ying Li
- Lizhuang Yang
- Ying Chen
- Ling Zuo
- Jia-Hong Gao
- Jianqiao Ge
- Guoyuan Yang
- Guangbin Cui
- Wen Wang
- Linfeng Yan
- Yang Yang
- Jin Zhang
- Junfang Xian
- Qian Wang
- Xiaoxia Qu
- Ying Wang
- Quan Zhang
- Fei Yuan
- Dawei Wang
- Li Hu
- Jizhen Li
- Yanwei Miao
- Weiwei Wang
- Yujing Zhou
- Wen Shen
- Miaomiao Long
- Lihua Liu
- Yongqiang Yu
- Xiaohu Li
- Xiaoshu Li
- Jiance Li
- Yunjun Yang
- Nengzhi Xia
- Weihua Liao
- Shuai Yang
- Youming Zhang
- Jing Zhang
- Guangyao Liu
- Laiyang Ma
- Hui Zhang
- Xiaochun Wang
- Ying Lei
- Bo Gao
- Gang Zhang
- Kang Yuan
- Xiaojun Xu
- Jingjing Xu
- Xiaojun Guan
- Feng Chen
- Yuankai Lin
- Huijuan Chen
- Zhihan Yan
- Yuchuan Fu
- Yi Lu
- Tong Han
- Jun Guo
- Hao Lu
- Zhenwei Yao
- Yue Wu
- Su Lui
- Jane Marie Smith
1 Application
| Application ID | Title |
|---|---|
| 75556 | Trans-ethnic genome-wide and exposome-wide association studies of neuroimaging and behavioral phenotypes |
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