Shared genetic etiology and causality between body fat percentage and cardiovascular diseases: a large-scale genome-wide cross-trait analysis

BMC Medicine

Zhenhuang Zhuang¹  Tao Huang²  Zhonghua Liu³  Minhao Yao³  Jason Y. Y. Wong⁴ 

[1] Department of Epidemiology & Biostatistics, School of Public Health, Peking University, China. 38 Xueyuan Road, 100191, Beijing, China;Department of Epidemiology & Biostatistics, School of Public Health, Peking University, China. 38 Xueyuan Road, 100191, Beijing, China;Center for Intelligent Public Health, Academy for Artificial Intelligence, Peking University, 100191, Beijing, China;Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, 100191, Beijing, China;Department of Statistics and Actuarial Science, The University of Hong Kong, Hong Kong, China;Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA;

关键词: Body fat percentage;    Cardiovascular diseases;    Shared genetics;    Genetic correlation;    Mendelian randomization;   

DOI  :  10.1186/s12916-021-01972-z

来源: Springer

【 摘 要 】

BackgroundAccumulating evidences have suggested that high body fat percentage (BF%) often occurs in parallel with cardiovascular diseases (CVDs), implying a common etiology between them. However, the shared genetic etiology underlying BF% and CVDs remains unclear.MethodsUsing large-scale genome-wide association study (GWAS) data, we investigated shared genetics between BF% (N = 100,716) and 10 CVD-related traits (n = 6968-977,323) with linkage disequilibrium score regression, multi-trait analysis of GWAS, and transcriptome-wide association analysis, and evaluated causal associations using Mendelian randomization.ResultsWe found strong positive genetic correlations between BF% and heart failure (HF) (Rg = 0.47, P = 1.27 × 10− 22) and coronary artery disease (CAD) (Rg = 0.22, P = 3.26 × 10− 07). We identified 5 loci and 32 gene-tissue pairs shared between BF% and HF, as well as 16 loci and 28 gene-tissue pairs shared between BF% and CAD. The loci were enriched in blood vessels and brain tissues, while the gene-tissue pairs were enriched in the nervous, cardiovascular, and exo-/endocrine system. In addition, we observed that BF% was causally related with a higher risk of HF (odds ratio 1.63 per 1-SD increase in BF%, P = 4.16 × 10–04) using a MR approach.ConclusionsOur findings suggest that BF% and CVDs have shared genetic etiology and targeted reduction of BF% may improve cardiovascular outcomes. This work advances our understanding of the genetic basis underlying co-morbid obesity and CVDs and opens up a new way for early prevention of CVDs.

【 授权许可】

CC BY