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

Abstract

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.

Effects of Long‐Term Regular Continuous and Intermittent Walking on Oxidative Stress, Metabolic Profile, Heart Rate Variability, and Blood Pressure in Older Adults with Hypertension

“…%BF has also been shown to be a risk factor for CVD and metabolic syndrome in both men and women, independent of BMI [ 60 ]. Targeted reduction of %BF may improve cardiovascular outcomes [ 61 ]. To our knowledge, few studies have investigated the effects of intermittent, low-intensity exercise, and most studies have incorporated continuous, low-intensity exercise.…”

Evaluating the Causal Association Between Educational Attainment and Asthma Using a Mendelian Randomization Design

“…For univariable MR analysis, we selected the inverse-variance weighted (IVW) as the main MR analysis method. Meanwhile, we also selected other additional MR analysis methods, including weighted median, MR-Egger method, and MR-PRESSO, as used in recent MR studies ( Bowden et al, 2015 ; Burgess and Thompson, 2017 ; Liu et al, 2018 ; Larsson et al, 2020 ; Au Yeung et al, 2021b ; Sun et al, 2021 ; Yuan et al, 2021 ; Zhao and Schooling, 2021 ; Zhuang et al, 2021b ). For multivariable MR analysis, we selected the multivariable IVW method, multivariable median-based method, and multivariable MR-Egger method.…”

“…Both assumption 2 and assumption 3 are known as no pleiotropy, as described in recent MR studies (Larsson et al, 2020;Au Yeung et al, 2021b;Sun et al, 2021;Yuan et al, 2021;Zhao and Schooling, 2021;Zhuang et al, 2021b). Hence, we conducted a pleiotropy analysis using the MR-Egger intercept test (Bowden et al, 2015;Burgess and Thompson, 2017) and the MR pleiotropy residual sum and outlier (MR-PRESSO) test (Verbanck et al, 2018); both have widely used in recent MR studies (Larsson et al, 2020;Au Yeung et al, 2021b;Sun et al, 2021;Yuan et al, 2021;Zhao and Schooling, 2021;Zhuang et al, 2021b). The significance threshold P < 0.05 indicated evidence of pleiotropy.…”

Shared Genetics and Causality Between Decaffeinated Coffee Consumption and Neuropsychiatric Diseases: A Large-Scale Genome-Wide Cross-Trait Analysis and Mendelian Randomization Analysis

“…For each locus, we extracted variants within 500 kb of the index SNP. The probability H4 was calculated in this method and the co-localized loci were defined with a probability >0.5 (29)(30)(31)(32)(33).…”