Abstract P550: Genome-Wide Association Analysis Identified Genetic Variants Associated With Cardiac Structure and Function in the Hispanic Community Health Study/Study of Latinos

Introduction: The role of genetic variants on cardiac structure and function among the Hispanic/Latino population is unclear. Hypothesis: We hypothesize that common genetic variants are associated with cardiac structure and function measures in the Hispanic/Latino population. Methods: We performed genome-wide association analyses of nine echo measures among individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), including: left ventricular end-systolic volume (LVESV), LV end-diastolic volume, mean wall thickness, LV mass index, LV ejection fraction (LVEF), stroke volume (SV), septal early mitral annular velocity, ratio of early ventricular filling peak velocity to early mitral annular velocity, and left atrial volume index. We further conducted enrichment analysis to locate candidate gene pathways and performed replication using data from UK BioBank (UKB) and BioBank of Japan (BBJ). Results: We included 4471 Hispanic/Latino participants from two sub-cohorts of HCHS/SOL (mean age 55 and 59, 68% female). Fourteen previously unreported variants at 3 loci were associated with LVEF, SV, or LVESV (p-value < 5х10 -8 , Figure ). Twelve of the 14 variants were associated with LVEF, located on or nearby ncRNA gene LOC105374813 , as well as 1 SNP on gene IPO5 with SV and 1 SNP on gene PGBD5 with LVESV. There were 199 variants that reached suggestive significance (p<5х10 -7 ) for nine measures, with most SNPs had effect directions consistent compared to UKB and BBJ findings. FUMA enrichment analysis showed SNP associated with SV on IPO5 had higher expression in kidney, liver, and heart tissue compared to other tissues. For variants associated with LVEF, eQTL analysis with heart tissue showed that gene RP11-342K6.2 and GCFC2 had chromatin interaction in the region. Conclusions: We identified 14 loci associated with cardiac structure and function among Hispanics/Latinos, providing supporting evidence of genetic contribution to cardiac dysfunction in Hispanic/Latino populations.