title: Prediction of blood pressure changes over time and incidence of hypertension by a genetic risk score in Swedes.
abstract: 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 Malmö 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 (β ± SEM, 0.968 ± 0.102 mm Hg and 0.585 ± 0.064 mm Hg; P<1E-19 for both) and at reinvestigation (β ± 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 (Δ) in BP (β ± 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.
authors.affiliation: Department of Clinical Sciences, Lund University, University Hospital of Malmö, Sweden. cristiano.fava@med.lu.se
authors.forename: Cristiano
authors.initials: C
authors.lastname: Fava
authors.forename: Marketa
authors.initials: M
authors.lastname: Sjögren
authors.forename: Martina
authors.initials: M
authors.lastname: Montagnana
authors.forename: Elisa
authors.initials: E
authors.lastname: Danese
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.forename: Gunnar
authors.initials: G
authors.lastname: Engström
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.forename: Gian Cesare
authors.initials: GC
authors.lastname: Guidi
authors.forename: Pietro
authors.initials: P
authors.lastname: Minuz
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011446:Prospective Studies; D013548:Sweden / Q000453:epidemiology