Epigenomics Lectures L 6 . 1 Search for genetic variants influencing cardiac hypertrophy — an integrative genomics approach

The left ventricular hypertrophy which is commonly observed in aortic stenosis develops as an adaptive response to pressure overload and itself is an independent major risk factor for morbidity and mortality. Previous studies have demonstrated a poor correlation between the degree of aortic stenosis or other clinical factors and the degree of left ventricular hypertrophy. The absence of a clear relation between the stenosis-dependent pressure load on the degree of left ventricular hypertrophy suggests that the left ventricular phenotype is dependent on a polygenic background. Familial predisposition of left ventricular hypertrophy is supported by several studies. In a recent genome-wide association study (GWAS) we found evidence for association between variation in left ventricular mass index and several chromosomal regions. We postulate that these chromosomal regions harbor genes that contribute to the development of heart hypertrophy in individuals with aortic stenosis. In this project we use an integrative genomics approach that combines GWAS results and informative SNP linkage disequilibrium maps with transcriptome sequencing data to identify novel genes and biological pathways affecting cardiac hypertrophy that could not be identified using GWAS alone. L6.2