Abstract 13489: Sex Differences in the Association of Multi-Ethnic Genome-Wide Systolic Blood Pressure Polygenic Risk Score With Hypertension

Introduction: Hypertension affects about half the US adult population with a higher prevalence in males. This study examines the contribution of the genetic architecture to the sex-associated differences in hypertension in a multi-ethnic US population.

Methods: Multi-ancestry genome-wide association studies for systolic blood pressure (SBP) were conducted for each sex separately in the UK BioBank. Sex-specific SBP polygenic risk scores (SBP-PRS), comprising 1.1 million variants each, were generated from these GWASs. Sex-specific SBP-PRS was calculated in participants who underwent whole genome sequencing in the All of Us project. Based on the SBP-PRS, the cohort was stratified into low (<2.5 ^th centile), low-intermediate (2.5 ^th -20 ^th centile), intermediate (20 ^th -80 ^th centile), high-intermediate (80 ^th -97.5 ^th centile), and high (>97.5 ^th centile) genetic risk of SBP. Hypertension was defined as a BP ≥130/80 mmHg or anti-hypertensive use. Logistic regression models were used to assess the sex-stratified association of SBP-PRS with hypertension.

Results: The All of Us cohort had 212,669 individuals [median age: 54 (38, 65) years] comprising 127,679 (60.0%) females and 97,600 (45.9%) non-White individuals (20.6% Black, 3.3% Asian, and 19.1% Hispanic). Hypertension was reported in 118,984 (55.9%) in the overall population and in 53,307 (62.7%) males and 65,677 (51.4%) females. Females [OR _adj : 1.29 (1.27-1.30)] had higher odds of developing hypertension per SD increase in SBP PRS compared with males [OR _adj : 1.22 (1.20-1.23)]. (P _interaction :2.5x10 ^-6 ) On stratification by SBP-PRS, females in the high-risk group and the low-risk group had higher odds of developing hypertension [OR _adj : 1.81 (1.68-1.95) vs. 1.61 (1.46-1.74)] and lower odds of hypertension [OR _adj : 0.52 (0.48-0.56) vs. 0.65 (0.60-0.71)], respectively compared with males.

Conclusion: The contributions of the genetic underpinnings to the development of hypertension vary by sex.