Heritability and genome-wide association analysis of renal sinus fat accumulation in the Framingham Heart Study

Abstract

Abstract Background Ectopic fat accumulation in the renal sinus is associated with chronic kidney disease and hypertension. The genetic contributions to renal sinus fat accumulation in humans have not been well characterized. Methods The present analysis consists of participants from the Framingham Offspring and Third Generation who underwent computed tomography; renal sinus fat and visceral adipose tissue (VAT) were quantified. Renal sinus fat was natural log transformed and sex- and cohort-specific residuals were created, adjusted for (1) age, (2) age and body mass index (BMI), and (3) age and VAT. Residuals were pooled and used to calculate heritability using variance-components analysis in SOLAR. A genome-wide association study (GWAS) for renal sinus fat was performed using an additive model with approximately 2.5 million imputed single nucleotide polymorphisms (SNPs). Finally, we identified the associations of renal sinus fat in our GWAS results with validated SNPs for renal function (n = 16), BMI (n = 32), and waist-to-hip ratio (WHR, n = 14), and applied a multi-SNP genetic risk score method to determine if the SNPs for each renal and obesity trait were in aggregate associated with renal sinus fat. Results The heritability of renal sinus fat was 39% (p Conclusions Renal sinus fat is a heritable trait, even after accounting for generalized and abdominal adiposity. This provides support for further research into the genetic determinants of renal sinus fat. While our study was underpowered to detect genome-wide significant loci, our candidate gene BMI risk score results suggest that variability in renal sinus fat may be associated with SNPs previously known to be associated with generalized adiposity.