Shared genetic architecture contributes to risk of major cardiovascular diseases

The extensive co-occurrence of cardiovascular diseases (CVDs), as evidenced by epidemiological studies, is supported by positive genetic correlations identified in comprehensive genetic investigations, suggesting a shared genetic basis. However, the precise genetic mechanisms underlying these associations remain elusive. By assessing genetic correlations, genetic overlap, and causal connections, we aim to shed light on common genetic underpinnings among major CVDs. Employing multi-trait analysis, we pursue diverse strategies to unveil shared genetic elements, encompassing SNPs, genes, gene sets, and functional categories with pleiotropic implications. Our study systematically quantifies genetic overlap beyond genome-wide genetic correlations across CVDs, while identifying a putative causal relationship between coronary artery disease (CAD) and heart failure (HF). We then pinpointed 38 genomic loci with pleiotropic influence across CVDs, of which the most influential pleiotropic locus is located at the LPA gene. Notably, 12 loci present high evidence of multi-trait colocalization and display congruent directional effects. Examination of genes and gene sets linked to these loci unveiled robust associations with circulatory system development processes. Intriguingly, distinct patterns predominantly driven by atrial fibrillation, coronary artery disease, and venous thromboembolism underscore the significant disparities between clinically defined CVD classifications and underlying shared biological mechanisms, according to functional annotation findings.

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Publication Details

Journal
Nature Communications
Published
2025-09-24
DOI
https://doi.org/10.1038/s41467-025-62419-0
Citations
2
Primary Topic
Genetic Associations and Epidemiology
Type
article
Field-Weighted Citation Impact
3.63

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article

Shared genetic architecture contributes to risk of major cardiovascular diseases

Siim Pauklin, Liuyang Cai, Jun Qiao, Rong Zhao et al.
2 citations
Nature Communications
Genetic Associations and Epidemiology
3.63
article

Shared genetic architecture contributes to risk of major cardiovascular diseases

Siim Pauklin, Liuyang Cai, Jun Qiao, Rong Zhao, Miaoran Chen, Minjing Chang, Shan Song, Sakthivel Sadayappan, Shifang Ding, Jinguo Xu, Can Wang, Yuhui Zhao, Ning Tan, Zeyang Liu, Pengcheng He, Lei Jiang, Yuliang Feng
article en
2 citations

Abstract

The extensive co-occurrence of cardiovascular diseases (CVDs), as evidenced by epidemiological studies, is supported by positive genetic correlations identified in comprehensive genetic investigations, suggesting a shared genetic basis. However, the precise genetic mechanisms underlying these associations remain elusive. By assessing genetic correlations, genetic overlap, and causal connections, we aim to shed light on common genetic underpinnings among major CVDs. Employing multi-trait analysis, we pursue diverse strategies to unveil shared genetic elements, encompassing SNPs, genes, gene sets, and functional categories with pleiotropic implications. Our study systematically quantifies genetic overlap beyond genome-wide genetic correlations across CVDs, while identifying a putative causal relationship between coronary artery disease (CAD) and heart failure (HF). We then pinpointed 38 genomic loci with pleiotropic influence across CVDs, of which the most influential pleiotropic locus is located at the LPA gene. Notably, 12 loci present high evidence of multi-trait colocalization and display congruent directional effects. Examination of genes and gene sets linked to these loci unveiled robust associations with circulatory system development processes. Intriguingly, distinct patterns predominantly driven by atrial fibrillation, coronary artery disease, and venous thromboembolism underscore the significant disparities between clinically defined CVD classifications and underlying shared biological mechanisms, according to functional annotation findings.

Nature CommunicationsVol. 16(1)
Shanxi Medical University (CN), Anhui Medical University (CN), Peking University (CN), Nuffield Orthopaedic Centre (GB), Southern University of Science and Technology (CN), University of Oxford (GB), Peking University First Hospital (CN), Second Hospital of Shanxi Medical University (CN), First Affiliated Hospital of Anhui Medical University (CN), Second Affiliated Hospital of Nanjing Medical University (CN), University of Hong Kong - Shenzhen Hospital (CN), Central Hospital of Wuhan (CN), Guangdong Academy of Medical Sciences (CN), Wuhan General Hospital of Guangzhou (CN), Guangdong Provincial People's Hospital (CN), Southern Medical University (CN), University of Cincinnati (US), South China University of Technology (CN)
Cancer Research UK, National Natural Science Foundation of China, Anhui Medical University, Natural Science Foundation of Guangdong Province, Science, Technology and Innovation Commission of Shenzhen Municipality, Southern University of Science and Technology, Natural Science Foundation of Xinjiang, Guangdong Provincial People's Hospital, National Science and Technology Major Project, Young Scientists Fund, Basic and Applied Basic Research Foundation of Guangdong Province
Openalex Percentile: Top 7%
Genetic Associations and Epidemiology
3.63
DOIOpen Access PDFOpenAlex
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