Development of a genetic risk score to predict the risk of hypertension in European adolescents from the HELENA study

Abstract

Abstract Background: Several single nucleotide polymorphisms (SNPs) have previously been associated with blood pressure (BP) levels, in adults and children. A combination of SNPs, forming a genetic risk score (GRS) could be considered as a useful genetic tool to identify individuals at risk of developing hypertension from early stages in life. Therefore, the aim of our study was to build a GRS being able to predict the genetic predisposition to hypertension in European adolescents. Methods: Data were extracted from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study. A total of 869 adolescents (53 % female), aged 12.5-17.5, with complete genetic and BP information were included. The sample was divided into altered (³ 130 mmHg for systolic and/or ³ 80 mmHg for diastolic) or normal BP. Based on the literature, a total of 1.534 SNPs from 57 candidate genes related with BP were selected from the HELENA genome wide association study database.Results: From 1534 SNPs available, An initial screening of SNPs univariately associated with BP (p < 0.10) was established, to finally obtain a number of 16 SNPs significantly associated with BP (p < 0.05) in the multivariate model. The unweighted GRS (uGRS) and weighted GRS (wGRS) were estimated. To validate the GRSs, the area under the curve was explored using ten-fold internal cross-validation for uGRS (0.796) and wGRS (0.803). Further covariates of interest were added to the analyses, obtaining a higher predictive ability.Conclusions: Both GRSs, could be useful to evaluate the genetic predisposition to hypertension in European adolescents.