Abstract Body (Do not enter title and authors here): Background: Hypertension (HTN) is a common cardiovascular condition that is associated with an increased risk of experiencing heart disease. Chronic pressure overload due to HTN can induce cardiac hypertrophy, which may present in the form of concentric (thickening of the heart walls) or eccentric (expansion of the heart cavity) hypertrophy. Both HTN and cardiac hypertrophy are independent risk factors for experiencing heart failure and co-incident HTN and cardiac hypertrophy exacerbates that heart failure risk. If we can identify those who are most at risk for experiencing cardiac hypertrophy in the presence of HTN, early preventative measures may be initiated to minimize the progression toward heart failure. In this study, we sought to identify if common genetic variants associated with cardiac hypertrophy in the presence of hypertension. Methods: A multi-ancestry cohort (N=82180) consisting of individuals with short-read whole genome sequencing data and an occurrence of essential HTN in their medical record was constructed from the All of Us version 7 dataset. Cardiac hypertrophy – defined as an occurrence of cardiomegaly, left ventricular hypertrophy, hypertrophic cardiomyopathy, or dilated cardiomyopathy – was excluded from controls (N=72960, mean age at initial HTN=58, 56% female) or included in cases (N=9220, mean age at initial HTN=60, 50% female). Genome-wide association studies (GWAS) were conducted using logistic multivariate regression models to test for associations between variants and hypertensive cardiac hypertrophy. These GWAS were stratified by ancestry, included three principal components, and were adjusted by sex and age at initial HTN. Results: European ancestry GWAS identified three genome-wide significant and four suggestive significant variants in the ARVCF gene. Ancestry stratification confirmed that statistical or suggestive associations between ARVCF variants and hypertensive cardiac hypertrophy were observed only in those of European ancestry. None of these variants have previously reported associations with HTN or cardiac hypertrophy. Conclusion: We have discovered loci in the ARVCF gene that associate with hypertensive cardiac hypertrophy among Europeans in the All of Us research program. We intend to replicate our work in other large European cohorts to confirm the potential value of this gene for future biomedical studies.