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

• Published in: BMC medicine Vol. 19; no. 1; p. 100
• Main Authors: Zhuang, Zhenhuang, Yao, Minhao, Wong, Jason Y Y, Liu, Zhonghua, Huang, Tao
• Format: Journal Article
• Language: English
• Published: England BioMed Central 29.04.2021; BMC
• Subjects: Adipose Tissue; Association analysis; Binding sites; Blood vessels; Body fat; Body fat percentage; Body mass index; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - genetics; Congestive heart failure; Consortia; Coronary artery; Coronary artery disease; Coronary vessels; Correlation analysis; Endocrine system; Estimates; Etiology; Gene expression; Gene loci; Genetic correlation; Genetic Predisposition to Disease; Genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Heart failure; Humans; Linkage disequilibrium; Mendelian randomization; Mendelian Randomization Analysis; Meta-analysis; Phenotype; Polymorphism, Single Nucleotide; Quality control; Shared genetics; Software; Stroke; Tissues; Transcriptomes; Body fat percentage; Genetic correlation; Mendelian randomization; Cardiovascular diseases; Shared genetics
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-021-01972-z

Accumulating 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. Using 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. We found strong positive genetic correlations between BF% and heart failure (HF) (Rg = 0.47, P = 1.27 × 10 ) and coronary artery disease (CAD) (Rg = 0.22, P = 3.26 × 10 ). 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. Our 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.