Prediction Of Blood Pressure Changes Over Time And Incidence Of Hypertension By A Genetic Risk Score In Swedes

Recent Genome Wide Association Studies (GWAS) have pinpointed different single nucleotide polymorphisms (SNPs) consistently associated with blood pressure (BP) and hypertension prevalence. However, little data exist regarding SNPs predicting BP variation over time and hypertension incidence. The aim of this study was to confirm the association of a genetic risk score (GRS), based on 29 independent SNPs, with cross sectional BP and hypertension prevalence and to challenge its prediction of BP change over time and hypertension incidence in more than 17,000 middle-aged Swedes participating in a prospective study, the “Malmö Preventive Project” (MPP), investigated at baseline and over a 23-year average period of follow-up. The GRS was associated with higher systolic and diastolic BP values both at baseline (ß±SEM 0.968±0.102mmHg and 0.585±0.064mmHg; p<1E-19 for both) and at reinvestigation (ß±SEM 1.333±0.161mmHg and 0.724±0.086mmHg; p<1E-15 for both) and with increased hypertension prevalence (OR [95%CI] 1.192 [1.140-1.245] and 1.144 [1.107-1.183]; p<1E-15 for both). The GRS was positively associated with change (Δ) in BP (ß±SEM 0.033±0.008mmHg/year and 0.023±0.004mmHg/year; p<1E-04 for both) and hypertension incidence (OR 95%CI 1.110 (1.065-1.156) p=6.7 E-07), independently from traditional risk factors. The relative weight of the GRS was lower in magnitude than obesity or pre-hypertension, but comparable to diabetes mellitus or a positive family history of hypertension (PFH). A C-statistics analysis does not show any improvement in the prediction of incident hypertension on top of traditional risk factors. Our data from a large cohort study show that a GRS is independently associated with BP increase and incidence of hypertension.