Genome‐wide association study of cardiometabolic multimorbidity in the UK Biobank

Chenxuan Zhao; Tianqi Ma; Xunjie Cheng; Gaoyan Zhang; Yushi Bai

doi:10.1111/cge.14513

journal article Feb 26, 2024

Genome‐wide association study of cardiometabolic multimorbidity in the UK Biobank

Chenxuan Zhao

Tianqi Ma Xunjie Cheng Gaoyan Zhang

Yushi Bai

Clinical Genetics Vol. 106 No. 1 pp. 72-81 · Wiley

View at Publisher Save 10.1111/cge.14513

Abstract

AbstractConsidering the high prevalence and poor prognosis of cardiometabolic multimorbidity (CMM), identifying causal factors and actively implementing preventive measures is crucial. However, Mendelian randomization (MR), a key method for identifying the causal factors of CMM, requires knowledge of the effects of SNPs on CMM, which remain unknown. We first analyzed the genetic overlap of single cardiometabolic diseases (CMDs) using the latest genome‐wide association study (GWAS) for evidential support and comparison. We observed strong positive genetic correlations and shared loci among all CMDs. Further, GWAS and post‐GWAS analyses of CMM were performed in 407 949 European ancestry individuals from the UK Biobank. Eleven loci and 12 lead SNPs were identified. By comparison, we found these SNPs were a subset of SNPs associated with CMDs, including both shared and non‐shared SNPs. Then, the polygenic risk score model predicted the risk of CMM (C‐index = 0.62) and we identified candidate genes related to lipid metabolism and immune function. Finally, as an example, two‐sample MR analysis based on the GWAS revealed potential causal effects of total cholesterol, serum urate, body mass index, and smoking on CMM. These results provide a basis for future MR research and inspire future studies on the mechanism and prevention of CMM.

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Metrics

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Citations

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References

Details

Published: Feb 26, 2024
Vol/Issue: 106(1)
Pages: 72-81
License: View

Authors

C

Chenxuan Zhao

Department of Cardiovascular Medicine, The Third Xiangya Hospital Central South University Changsha China; Department of Geriatric Medicine, Center of Coronary Circulation, Xiangya Hospital Central South University Changsha China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University Changsha China

T

Tianqi Ma

Department of Geriatric Medicine, Center of Coronary Circulation, Xiangya Hospital Central South University Changsha China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University Changsha China

X

Xunjie Cheng

Department of Geriatric Medicine, Center of Coronary Circulation, Xiangya Hospital Central South University Changsha China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University Changsha China

G

Gaoyan Zhang

Department of Cardiovascular Medicine, The Third Xiangya Hospital Central South University Changsha China; Department of Cardiovascular Medicine, Xiangya Hospital Central South University Changsha China

Y

Yushi Bai

Department of Geriatric Medicine, Center of Coronary Circulation, Xiangya Hospital Central South University Changsha China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University Changsha China

Funding

National Key Research and Development Program of China Award: 2020YFC2008002

Cite This Article

Chenxuan Zhao, Tianqi Ma, Xunjie Cheng, et al. (2024). Genome‐wide association study of cardiometabolic multimorbidity in the UK Biobank. Clinical Genetics, 106(1), 72-81. https://doi.org/10.1111/cge.14513

Genome‐wide association study of cardiometabolic multimorbidity in the UK Biobank

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