Proteomic organ-specific signatures, ageing traits, disease risks and genetic architecture in an East Asian population

作者：Derrick Bennett, Derrick Bennett, Baihan Wang, Sihao Xiao, Neil Wright, Ahmed Edris, Yunhe Wang, Iona Y. Millwood, Robin Walters, Huaidong Du, Ling Yang, Yiping Chen, Daniel Avery, Dan Valle Schmidt, Canqing Yu, Dianjianyi Sun, Jun Lv, Michael Hill, Liming Li, Robert Clarke, Junshi Chen, Zhengming Chen, Junshi Chen, Zhengming Chen, Zhengming Chen, Rory Collins, Liming Li, Jun Lv, Richard Peto, Robin Walters, Canqing Yu, Dianjianyi Sun, Derrick Bennett, Derrick Bennett, Daniel Avery, Maxim Barnard, Derrick Bennett, Derrick Bennett, Ruth Boxall, Ka Hung Chan, Yiping Chen, Zhengming Chen, Zhengming Chen, Jonathan Clarke, Huaidong Du, Ahmed Edris Mohamed, Hannah Fry, Yani Huang, Pek Kei Im, Andri Iona, Christiana Kartsonaki, Kshitij Kolhe, Thu Pam, Kuang Lin, Iona Millwood, Sam Morris, Qunhua Nie, Sara Perez Vizan, Thu Pam, Alfred Pozarickij, Maryam Rahmati, Paul Ryder, Maruf Sarder, Dan Valle Schmidt, Roshi Shrestha, Becky Stevens, Robin Walters, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Pang Yao, Liming Li, Jun Lv, Chao Liu, Dianjianyi Sun, Lang Pan, Xiao Han, Can Hou, Qingmei Xia, Chao Liu, Pei Pei, Lang Pan, Xiao Han, Haiping Duan, Xinxin Chen, Zengchang Pang, Ruqin Gao, Ke Lv, Shanpeng Li, Haiping Duan, Shaojie Wang, Yongmei Liu, Ranran Du, Liang Cheng, Xiaocao Tian, Hua Zhang, Dan Hu, Xiaoyan Zheng, Yujie Wang, Wei Sun, Shichun Yan, Yong Zhou, Chi Wang, Zhenyuan Wu, Lishun Zhai, Xingren Wang, Shiwen Dong, Li Liu, Dapeng Yin, Bin He, Lihui Li, Xingren Wang, Yan Xu, Xiangyang Zheng, Dewei Zheng, Shuai Yang, Lihui Li, Xuejia Chen, Yan Xu, Jinyi Zhou, Ran Tao, Jian Su, Xikang Fan, Xuejia Chen, Yuxiao Huang, Yan Lu, Yujie Hua, Li Xing, S.C. Wang, Jianrong Jin, Juping Ma, Kaifei Zhu, Hongfu Ren, Xingfeng Shen, Ge Zhong, Wei Mao, Zhenzhen Lu, Yanxu Zhong, Lifang Zhou, Rong Pan, Jian Lan, 伍贤平, Jinxue Tan, Yishan Xie, Liuping Wei, Liyuan Zhou, Sisi Wang, 伍贤平, Ningmei Zhang, Xiaofang Chen, 常笑语, Zhuo Wang, Yujin He, Mingqiang Yuan, Ling Wang, Xiaofang Chen, Zhaodong Wang, Qiang Sun, Yang Lin, Faqing Chen, Xiaolan Ren, Lijun Chang, Feiming Zhong, Jianjun Feng, Weijie Hu, Xiaofang Zhang, Yalin Chen, Honghong Wang, Wenjie Yang, Linqi Diao, Yali Yan, Dengjun Zhu, Kai Kang, Shixian Feng, Wenjie Yang, Huizi Tian, Yali Yan, Bing Han, Li Gao, Shaofang Li, Tianfang Xing, Wei Tang, Lei Fan, Xiaolin Li, Huarong Sun, Xiaocong Zhao, Ying Li, Ruying Hu, Hao Wang, Xukui Zhang, Yuanyuan Jin, Lan Luo, Chunxiao Xu, Ruying Hu, Hao Xu, Weiwei Gong, Jieming Zhong, Meng Wang, Xiaomei Tu, Keqing Gong, Hao Xu, Yuan Cao, Kaixu Xie, Lingli Chen, Xiaomei Tu, Junlong Pan, Xiaojun Li, Li Yin, Huilin Liu, Yuan Peng, Lei Yin, Xian Xie, Jing Wang, Bo Xiao, Zongwei Deng, Yuan Peng, Libo Zhang, Chan Qu, Li Deng, Qili Jiang, Yanling Chen · 发表于：EBioMedicine · 年份：2026 · DOI：10.1016/j.ebiom.2026.106401 · 研究领域：Advanced Proteomics Techniques and Applications、Mitochondrial Function and Pathology、Forensic and Genetic Research

BACKGROUND: Protein-based ageing clocks can be used to help identify individuals at high risk of death or morbidity. There is a lack of evidence in non-European populations on clocks derived from combining different proteomic platforms and their relationship with age-related traits, diseases and genetic architecture. METHODS: The prospective China Kadoorie Biobank assayed proteins via Olink and SomaScan in ∼4000 individuals with a mean age of 58 years. We used organ-enriched plasma proteins identified from the Genotype-Tissue Expression Project and trained Light Gradient Boosting models on chronological age (ChronAge) to derive protein organ age and age gaps (ProtAgeGap) for 18 organs. We then investigated their relationship with age-related traits and incident diseases after adjustment for multiple testing. Moreover, we conducted genome-wide association studies to identify genetic variants for overall and organ-specific ProtAgeGaps. FINDINGS: The overall proteomic and organ-specific ageing clocks for each platform combined for all participants were strongly related with ChronAge. The organ-specific and overall proteomic age were associated with age-related traits and a range of incident diseases independent of ChronAge. In particular, the kidney organ-specific ageing clock was associated with higher risk of stroke (1.03; 1.02-1.05), chronic liver disease (CLD, 1.11; 1.05-1.18); chronic kidney disease (CKD, 1.19; 1.11-1.27) per 1-year higher ProtAgeGap. GWAS of overall proteo...