Epigenomic profiles of African American Transthyretin Val122Ile carriers reveals putatively dysregulated amyloid mechanisms

The Val122Ile mutation in Transthyretin (TTR) gene causes a rare, difficult to diagnose hereditary form of cardiac amyloidosis. This mutation is most common in the United States and mainly present in people of African descent. The carriers have an increased risk of congestive heart failure, peripheral edema, and several other non-cardiac phenotypes such as carpal tunnel syndrome, and arthroplasty which are top reasons for ambulatory/outpatient surgeries in the country. We conducted first-ever epigenome-wide association study in Val122Ile carriers of African descent for heart disease (HD) and multiple outpatient surgeries (OS) - an early disease indicator. DNA was extracted from whole blood of Yale-Penn participants using the EZ-96 DNA methylation kit (Zymo Research, CA, USA). DNA methylation was assayed using the Illumina Infinium MethylationEPIC chip quantifying >850,000 CpG sites and imaged on the Illumina iScan system at YCGA. The methylation intensity data (*.idat files) was exported for analysis using the manufacturer's recommended protocol using the GenomeStudio methylation module. Epigenomic differences were tested with respect to the history of heart disease (N=90 controls; 6 cases; Males-47%) and 10 or more outpatient surgeries (N=94 controls, 2 cases; Males-46%) in 96 individuals who were carriers of Val122Ile mutation.