Objective: Recent Genome Wide association studies pinpointed different single nucleotide polymorphisms (SNPs) consistently associated with blood pressure (BP) and hypertension prevalence. Anyhow, scanty data exist about SNPs predicting BP variation over time and incidence of hypertension. The aim of our 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 about BP change over time and hypertension incidence in middle-aged Swedes participating in a prospective survey in Malmö (Sweden). Design and Methods: Twenty-nine SNPs were genotyped in 18,240 participants included in the “Malmö Preventive project”. The same subjects were investigated at baseline and over a period of an average of 23 years of follow-up. The GRS was calculated by summing the number of risk alleles across the panel of SNPs tested (0, 1, and 2 were attributed according to the number of risk alleles present). Results: The GRS was associated with higher systolic and diastolic BP values both at baseline and at reinvestigation and with increase prevalence of hypertension (p<1.0E-11 and lower for all). The GRS was positively associated with change in BP and the incidence of hypertension, independently from “traditional factors” (p<1.0E-4 and lower for all). The relative weight of the GRS [1st vs. 4th quartile OR (95%CI) 1.298 (1.161-1.452) p<1.0E-5] was lower compared to other well known predictors such as obesity and positive family history (PFH) but almost similar in magnitude as compared with diabetes mellitus, and higher with respect to chronic kidney disease and heart rate. Conclusions: Our data show that a GRS can help predicting BP variation and incidence of hypertension over time. The lower magnitude of the GRS, despite the well-known high heritability of all BP related traits, suggests that either many common SNPs influencing BP remain to be discovered or that rarer variants with higher effect on BP have a major impact also at population level.
Prediction of blood pressure change over time and incidence of hypertension by a genetic risk score in Swedes.
FAVA, Cristiano;MONTAGNANA, Martina;DANESE, Elisa;
2012-01-01
Abstract
Objective: Recent Genome Wide association studies pinpointed different single nucleotide polymorphisms (SNPs) consistently associated with blood pressure (BP) and hypertension prevalence. Anyhow, scanty data exist about SNPs predicting BP variation over time and incidence of hypertension. The aim of our 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 about BP change over time and hypertension incidence in middle-aged Swedes participating in a prospective survey in Malmö (Sweden). Design and Methods: Twenty-nine SNPs were genotyped in 18,240 participants included in the “Malmö Preventive project”. The same subjects were investigated at baseline and over a period of an average of 23 years of follow-up. The GRS was calculated by summing the number of risk alleles across the panel of SNPs tested (0, 1, and 2 were attributed according to the number of risk alleles present). Results: The GRS was associated with higher systolic and diastolic BP values both at baseline and at reinvestigation and with increase prevalence of hypertension (p<1.0E-11 and lower for all). The GRS was positively associated with change in BP and the incidence of hypertension, independently from “traditional factors” (p<1.0E-4 and lower for all). The relative weight of the GRS [1st vs. 4th quartile OR (95%CI) 1.298 (1.161-1.452) p<1.0E-5] was lower compared to other well known predictors such as obesity and positive family history (PFH) but almost similar in magnitude as compared with diabetes mellitus, and higher with respect to chronic kidney disease and heart rate. Conclusions: Our data show that a GRS can help predicting BP variation and incidence of hypertension over time. The lower magnitude of the GRS, despite the well-known high heritability of all BP related traits, suggests that either many common SNPs influencing BP remain to be discovered or that rarer variants with higher effect on BP have a major impact also at population level.
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