Abstract P181: The Genetic Epidemiology Of Longitudinal Blood Pressure Traits From Adolescence To Early Adulthood In Latinos

Abstract

Introduction: Blood pressure (BP) is known to rise during developmental stages from childhood to adulthood, and that those with higher BP trajectories are more likely to develop hypertension and CVD. Yet, there is a paucity of studies that have evaluated trajectories of BP change or the genetic factors involved in the BP changes from childhood to adulthood. Epidemiological and genetic epidemiological studies of longitudinal BP changes through the life-course may enable a better understanding of the pathogenesis of hypertension and may lead to the identification of loci associated with BP trajectories and CVD risk during this critical period. Methods: We leverage multiple self-identified Hispanic/Latino populations with longitudinal BP and genomic data across the lifecourse, in particular between adolescence and young adulthood. We present herein preliminary results from the Santiago longitudinal study (SLS) that enrolled infants of Hispanic ancestry and measured BP at late adolescence (average age of 16 years) and early adulthood (average age of 22 years) to identify genetic variants associated with trajectories of BP traits (systolic BP, diastolic BP, mean arterial pressure and pulse pressure). We conducted a complete case analysis excluding participants taking antihypertensive medications and those whose BP measures were statistical outliers. Linear mixed models were used to assess the trajectories of individual BP traits between late adolescence and early adulthood (n = 1236), adjusting for age, sex and BMI. We assessed the relationship between residuals and genetic variants adjusting for two ancestral principal components using SUGEN software. Results: Males constituted 51% of the total SLS cohort. Interestingly, with each year increase in age, we observed downward trajectories of both mean systolic BP (-0.3 mmHg, 95% CI (-0.4, -0.2)) and mean diastolic BP (-0.1 mmHg, 95% CI (-0.2, -0.04)) adjusted for BMI and sex. We identified evidence for five known BP loci and two suggestive new signals. Our most significant finding is rs10894989 [beta (SE) = 6.57 (1.26), p =1.86x10 -7 , minor allele frequency (EAF = 0.94)] near the ARHGAP42 gene, an established locus for hypertension. However, this variant is not in linkage disequilibrium with the commonly reported SNP rs604723 (r 2 = 0.04). Ancestry-specific allele frequencies differed with rs604723 more common in East Asians and Europeans and rs10894989 commonest in Africans. Conclusion: Our longitudinal analyses of BP from late adolescence to early adulthood replicated BP loci and identified novel suggestive loci associated with BP trajectories supporting a need for further GWAS of longitudinal BP. We are currently conducting a meta-analysis of longitudinal BP trajectories in 3,000 young adults self-identified as Hispanic Latino in the Population Architecture using Genomics and Epidemiology (PAGE) study.