Personal, social, and natural co-exposure pattern and plasma proteins in cardiometabolic diseases

Xuewei Tang, Huan Xu, Gonghua Wu, Shaokun Yang, Yonghua Ye, Yan An, Yilin Jiang, Zilong Wang, Sujun Chen, Juying Zhang (), Xiong Xiao (), Bing Guo () and Xing Zhao ()
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Xuewei Tang: Sichuan University, West China School of Public Health and West China Fourth Hospital
Huan Xu: Sichuan University, West China School of Public Health and West China Fourth Hospital
Gonghua Wu: Sichuan University, West China School of Public Health and West China Fourth Hospital
Shaokun Yang: Sichuan University, West China School of Public Health and West China Fourth Hospital
Yonghua Ye: Sichuan University, West China School of Public Health and West China Fourth Hospital
Yan An: Sun Yat-sen University, School of Life Sciences
Yilin Jiang: Kyoto University, Frontier and International Psychiatry, Graduate School of Medicine
Zilong Wang: New Territories, Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin
Sujun Chen: Sichuan University, West China School of Public Health and West China Fourth Hospital
Juying Zhang: Sichuan University, West China School of Public Health and West China Fourth Hospital
Xiong Xiao: Sichuan University, West China School of Public Health and West China Fourth Hospital
Bing Guo: Sichuan University, West China School of Public Health and West China Fourth Hospital
Xing Zhao: Sichuan University, West China School of Public Health and West China Fourth Hospital

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: Abstract Multiple environmental exposures elevate the risk of cardiometabolic diseases (CMDs), yet the impact of combined co-exposures, and their protein-mediated mechanisms remain underexplored. Among 366,261 UK Biobank participants, this study identified five distinct exposure patterns through clustering analysis: Air and Noise Pollution, Social Deprivation, Blue and Green Space, Health Behaviors and Reference. Notably, the Social Deprivation pattern showed the highest CMDs risk, with hazard ratios ranging from 1.15 to 1.40. Inflammatory and immune proteins were associated with all co-exposure patterns. The Air and Noise Pollution and Social Deprivation patterns demonstrated that the common mediating proteins included CDCP1, CXCL17, FGF21, GDF15 and IGFBP4. CXCL13, CA6, SDC1, and PTN mediated Healthy Behaviors, while MMP12 mediated Blue and Green Space pattern. This study offers etiological insight into the comprehensive human environment, draws attention to the population experiencing health disadvantages as a result of co-exposure to social stressors, and elucidates protein-mediated mechanisms linking environmental exposures to disease.

Date: 2025
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DOI: 10.1038/s41467-025-65516-2

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