journal article·2026-07-06Open access

Harnessing Large‐Scale Multi‐Omics Data for Risk Prediction and Deep Phenotyping of Valvular Heart Diseases in the General Population

Zhihao Jiang, Yang Liu, Mingyu Song, Ning Chen, Canqing Yu, Jun Lv, Eric Yuk Fai Wan, Lu Qi, Liming Li, Dianjianyi Sun, Bang Zheng

Abstract

ABSTRACT The risk profile of valvular heart disease (VHD) and its underlying mechanisms remain poorly understood. This study aimed to develop and validate a multi‐omics‐based risk prediction model, and to elucidate potential biological mechanisms. Using data from the UK Biobank, Cox proportional hazards and machine learning models (XGBoost and LightGBM) were evaluated for predicting VHD and its subtypes (aortic valve stenosis, AVS; aortic valve regurgitation, AVR; mitral valve regurgitation, MVR). Cox models based on key clinical factors showed the best predictive performance (C‐index of 0.75–0.81), which was further enhanced by incorporating proteomic data (all C‐index > 0.81) but not by genomic or metabolomic data. Notably, a simplified 10‐year model comprising only four top proteins maintained favorable performance (C‐index of 0.75–0.82). Cluster analysis identified blood pressure and lipid levels as leading modifiable risk factors for VHD onset. Functional enrichment analysis revealed that VHD is primarily associated with protease inhibition, AVS with fibrotic and matrix metabolic pathways, and MVR with immune‐inflammatory activation. Mendelian randomization and Bayesian colocalization analyses suggested causal associations between CNTN5 and CD8A with risks of AVS and MVR, whilst IGFBP7 showed a reverse‐direction association with AVS. These findings highlight promising avenues for early diagnostic biomarkers and potential precision‐targeted therapies.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Cardiac Valve Diseases and Treatments · Congenital heart defects research · Genetic Associations and Epidemiology

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Epidemiology and Biostatistics School of Public Health Peking University Beijing China

Peking University Center for Public Health and Epidemic Preparedness & Response Beijing China

Ministry of Education Key Laboratory of Epidemiology of Major Diseases (Peking University) Beijing China

State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Beijing China

Department of Family Medicine and Primary Care Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China

Centre for Safe Medication Practice and Research Department of Pharmacology and Pharmacy Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China

The Institute of Cardiovascular Science and Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China

Advanced Data Analytics for Medical Science Limited Hong Kong SAR China

Department of Epidemiology School of Public Health and Tropical Medicine Tulane University New Orleans Louisiana USA

Department of Nutrition Harvard T.H. Chan School of Public Health Harvard University Boston Massachusetts USA

Ageing Epidemiology Research Unit School of Public Health Imperial College London London UK

Department of Non‐communicable Disease Epidemiology London School of Hygiene & Tropical Medicine London UK

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China

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