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Background  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.    Methods  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.    Results  We 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.    Conclusions  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.

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