A NEW GENETIC RISK SCORE FOR BLOOD PRESSURE STRONGLY ASSOCIATES WITH THE INCIDENCE OF HYPERTENSION AND CARDIOVASCULAR ENDPOINTS IN TWO SWEDISH COHORTS

Abstract

Objective: The clinical value of the polygenetic component of blood pressure is commonly questioned. We constructed a new BP-GRS, including the most recently published variants genome wide significantly associated with either systolic or diastolic blood pressure (SBP, DBP), to investigate its association to the incidence of hypertension and cardiovascular endpoints in two urban-based cohorts: the Malmö Diet and Cancer (MDC, n = 29295) and Malmö Preventive Project (MPP, n = 9367). Design and method: The genotyping was performed with the Illumina GWAS chip (GSA array v1) and a weighted BP-GRS858 based on 858 SNPs was calculated, normalized, and divided into deciles. Logistic regression and survival Cox Regression models were used to test the associations of the new BP-GRS858 with outcomes. Results: At baseline, we found a difference of 11.2 mmHg (SBP) and 6 mmHg (DBP) between the top and the bottom deciles of BP-GRS858. In MPP, the top vs bottom decile of BP-GRS858 was associated with a doubled risk of incident hypertension (OR, 95%CI: 2.2, 1.7–2.8, p-value: 2.0E-10). In MDC, when comparing the top and bottom deciles of BP-GRS858, significant association was found between the age and sex adjusted BP-GRS858 and the incidence of total cardiovascular events (HR, 95%CI: 1.5; 1.3–1.7; p-value: 1.5E-12), stroke (HR, 95%CI: 1.6, 1.4–1.8; p-value: 2.1E-9), coronary artery disease (HR, 95%CI: 1.5, 1.4–1.8; p-value:1.3E-11), heart failure (HR, 95%CI: 1.5, 1.3–1.8, p-value: 2.5E-5), atrial fibrillation (HR, 95%CI: 1.2–1.1,1.4; p-value: 0.001) and total mortality (HR, 95%CI: 1.1, 1.0–1.2; p-value: 0.009). Most of these associations remained significant after adjusting for traditional risk factors, including hypertension. Conclusions: Our findings confirm that adding novel genetic variants into a polygenic BP-GRS, despite very low effect sizes of individual variants, increases its predictive performance. GRS858 contributes with clinically meaningful predictive information regarding future hypertension and CVD risk. Given that the exposure to high polygenetic risk starts at birth, we suggest that the BP-GRS858 might be useful to identify children or adolescents who would benefit from early hypertension screening and treatment.