RATIONALE: Hypertension affects 1 in 3 adults worldwide. A common outcome of hypertension is the development of cardiac hypertrophy. However, this response to hypertension is not universal as there is evidence of variability in the extent of hypertrophy and in whether it develops at all. This strongly implies the presence of genetic factors that may be explored to improve therapeutic and prognostic approaches to better manage outcomes of hypertension.
Recently, our group has discovered a novel, genome-wide significant association between hypertensive cardiac hypertrophy and ARVCF using data available in the All of Us research program. This proposal seeks to replicate that finding as well as expand these analyses into documented, yet unexplored human variants of ARVCF while utilizing a more refined measurement of cardiac hypertrophy in the UK Biobank’s large-scale MRI cardiac imaging data. Additionally, we found that this novel association may be mediated by susceptibility to renal dysfunction. As kidney disease and hypertension have a strong bidirectional relationship, this offers an exciting path to understand how ARVCF may connect to hypertensive cardiac hypertrophy. Therefore, we also intend to investigate associations between ARVCF and renal dysfunction markers using the UK Biobank’s prospective blood biochemistry assay data.
RESEARCH QUESTION: How do previously identified ARVCF genomic variants associate with the incidence of hypertensive cardiac hypertrophy, cardiac imaging-derived phenotypes, and renal dysfunction markers?
OBJECTIVE 1: To examine associations between previously identified ARVCF genomic variants and cardiac imaging-derived phenotypes.
OBJECTIVE 2: To examine associations between previously identified ARVCF genomic variants and renal dysfunction markers.