Key result
Genetically predicted differences in adiposity-adjusted pericardial adipose tissue were causally associated with adverse left ventricular remodeling, with 12 significant variants identified.
Why the study?
Greater pericardial adipose tissue (PAT) deposition might mediate cardiovascular disease independent of general or subcutaneous adiposity, motivating characterization of the genetic architecture of adiposity-adjusted PAT and its causal associations with adverse cardiac measures.
Observational (n=28,161)
p-value: p=4.20×10^-9 and 1.30×10^-12
This study identifies specific genetic variants associated with pericardial fat deposition and provides Mendelian randomization evidence that genetically determined pericardial fat is causally linked to adverse left ventricular remodeling.
No clinical targeting of pericardial fat yet; leaves open interventional confirmation of its causal role in LV remodeling.
BACKGROUND Pericardial adipose tissue (PAT) is the visceral adipose tissue compartment surrounding the heart. Experimental and observational research has suggested that greater PAT deposition might mediate cardiovascular disease, independent of general or subcutaneous adiposity. We characterize the genetic architecture of adiposity‐adjusted PAT and identify causal associations between PAT and adverse cardiac magnetic resonance imaging measures of cardiac structure and function in 28 161 UK Biobank participants. METHODS AND RESULTS The PAT phenotype was extracted from cardiac magnetic resonance images using an automated image analysis tool previously developed and validated in this cohort. A genome‐wide association study was performed with PAT area set as the phenotype, adjusting for age, sex, and other measures of obesity. Functional mapping and Bayesian colocalization were used to understand the biologic role of identified variants. Mendelian randomization analysis was used to examine potential causal links between genetically determined PAT and cardiac magnetic resonance–derived measures of left ventricular structure and function. We discovered 12 genome‐wide significant variants, with 2 independent sentinel variants (rs6428792, P =4.20×10 −9 and rs11992444, P =1.30×10 −12 ) at 2 distinct genomic loci, that were mapped to 3 potentially causal genes: T‐box transcription factor 15 ( TBX15 ), tryptophanyl tRNA synthetase 2, mitochondrial ( WARS2 ) and early B‐cell factor‐2 ( EBF2 ) through functional annotation. Bayesian colocalization additionally suggested a role of RP4‐712E4.1. Genetically predicted differences in adiposity‐adjusted PAT were causally associated with adverse left ventricular remodeling. CONCLUSIONS This study provides insights into the genetic architecture determining differential PAT deposition, identifies causal links with left structural and functional parameters, and provides novel data about the pathophysiological importance of adiposity distribution.
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Salih et al. (2023) conducted an observational in Pericardial adipose tissue deposition (n=28,161). Genetically determined pericardial adipose tissue (PAT) was evaluated on Genome-wide significant variants associated with PAT area (p=4.20×10^-9 and 1.30×10^-12). Genetically predicted differences in adiposity-adjusted pericardial adipose tissue were causally associated with adverse left ventricular remodeling, with 12 significant variants identified.
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