GENETIC DETERMINANTS OF BLOOD PRESSURE IN QATARI AND EUROPEAN POPULATIONS

Abstract

Blood pressure (BP) regulation is crucial for cardiovascular health, with hypertension (HTN) being a major risk factor for cardiovascular diseases worldwide. Though genome-wide association studies have identified numerous BP-associated variants, the underrepresentation of Middle Eastern (ME) populations in genetic studies limits the applicability of findings to this region. To address this, we investigated the genetic architecture of BP in a ME population using whole-genome sequencing data from the Qatar Genome Program (QGP). We identified some potentially unique BP-associations in the QGP cohort. Meta-analysis uncovered novel diastolic BP (DBP) associations which mapped to JARID2, EPS15, and NOL4L. Additionally, rare variant burden testing revealed potential associations of CPNE1, GNAT1, and ABCD2 with BP traits. Hypertensives show variability in BP and drug response due to both environmental and genetic factors. They may carry distinct subsets of BP-associated variants, forming specific subgroups based on the genetic factors and affected pathways, enabling more personalized treatment. We used the UK Biobank (UKBB) data and machine learning to predict HTN and stratify patients into subgroups based on predictive variants. Our model, incorporating genetic variants and known covariates, achieved 78% accuracy, and identified 405 SBP- and 325 DBP-associated variants predictive of HTN. Clustering hypertensive individuals based on these variants revealed 14 distinct subgroups for both systolic and diastolic HTN. These findings highlight previously unexplored associations and emphasize the need for including diverse populations in genetic studies to enhance personalized prevention and management strategies. Additionally, stratifying hypertensives based on HTN-predicting variants has the potential to advance personalized treatment approaches tailored to specific genetic profiles.

Date of Award	2024
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences