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 consistently associated with blood pressure ( BP) and hypertension prevalence. However, little data exist regarding single nucleotide polymorphisms 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 single nucleotide polymorphisms, with cross-sectional BP and hypertension prevalence and to challenge its prediction of BP change over time and hypertension incidence in >17 000 middle-aged Swedes participating in a prospective study, the Malmo Preventive Project, 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 (beta +/- SEM, 0.968 +/- 0.102 mm Hg and 0.585 +/- 0.064 mm Hg; P<1E-19 for both) and at reinvestigation (beta +/- SEM, 1.333 +/- 0.161 mm Hg and 0.724 +/- 0.086 mm Hg; P<1E-15 for both) and with increased hypertension prevalence (odds ratio [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 (Delta) in BP (beta +/- SEM, 0.033 +/- 0.008 mm Hg/y and 0.023 +/- 0.004 mm Hg/y; P<1E-04 for both) and hypertension incidence (odds ratio [ 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 prehypertension, but comparable with diabetes mellitus or a positive family history of hypertension. 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. (Hypertension. 2013;61:319-326.). circle Online Data Supplement