Abstract
Introduction: While previous studies have reported associations of pericardial adipose tissue (PAT) with cardiovascular diseases such as atrial fibrillation (AF) and coronary artery disease (CAD), they have been limited in sample size or drawn from selected populations. Additionally, the genetic determinants of PAT remain largely unknown. Hypothesis: PAT is associated with cardiovascular diseases and genetic loci influence variation in PAT. Methods: A deep learning model was trained to quantify PAT area from four-chamber CMR images in the UK Biobank using semantic segmentation. Cross-sectional and prospective cardiovascular disease associations were evaluated, controlling for sex and age. A genome-wide association study was performed, and a polygenic score (PGS) for PAT was examined in 453,733 independent FinnGen study participants. Results: A total of 44,725 UK Biobank participants (51.7% female, mean [SD] age 64.1 [7.7] years) were included. PAT was positively associated with male sex (β = +0.76 SD in PAT), age (r = 0.15), body mass index (BMI; r = 0.47) and waist-to-hip ratio (r = 0.55) (P < 1x10 -230 for all). PAT was more elevated in prevalent heart failure (β = +0.46 SD units) and type 2 diabetes (T2D; β = +0.56) than in CAD (β = +0.22) or AF (β = +0.18). Baseline PAT was associated with incident heart failure (HR = 1.29 per +1 SD in PAT [95% CI 1.17-1.43]) and T2D (HR = 1.63 [1.51-1.76]) during mean (SD) 3.2 (1.5) years of follow-up; the associations remained significant when controlling for BMI. We replicated 2/2 known genetic loci and identified 5 novel loci, implicating transcriptional regulators of adipocyte morphology and brown adipogenesis ( EBF1 , EBF2 and CEBPA ) and regulators of visceral adiposity ( WARS2 and TRIB2 ). The PAT PGS was associated with T2D, HF, CAD and AF in FinnGen (ORs 1.03-1.06 per +1 SD in PGS, P < 2x10 -10 for all). Conclusions: PAT shares genetic determinants with abdominal obesity and is an independent predictor of incident T2D and heart failure.
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