title: Association of uric acid genetic risk score with blood pressure: the Rotterdam study.
abstract: High levels of serum uric acid are associated with hypertension in observational studies. The aim of this study was to investigate the association of uric acid gene variants with blood pressure. We studied 5791 participants aged ≥55 years from the Rotterdam Study. Thirty gene variants identified for serum uric acid level were used to compile genetic risk score (GRS). We used linear regression models to investigate the association of the uric acid GRS with systolic and diastolic blood pressure in the whole study population and separately in participants with and without comorbidities and medication use. In the age- and sex-adjusted model, each SD increase in uric acid GRS was associated with 0.75 mm Hg lower systolic blood pressure (95% confidence interval, -1.31 to -0.19) and 0.42 mm Hg lower diastolic blood pressure (95% confidence interval, -0.72 to -0.13). The association did not attenuate after further adjustment for antihypertensive medication use and conventional cardiovascular risk factors. In subgroup analysis, the association of uric acid GRS with systolic blood pressure was significantly stronger in participants (n=885) on diuretic treatment (P for interaction, 0.007). In conclusion, we found that higher uric acid GRS is associated with lower systolic and diastolic blood pressure. Diuretics treatment may modify the association of uric acid genetic risk score and systolic blood pressure. Our study suggests that genome wide association study's findings can be associated with an intermediate factor or have a pleiotropic role and, therefore, should be applied for Mendelian Randomization with caution.
authors.affiliation: Departments of Epidemiology (S.S., R.P., A.G.U., A.H., B.H.Ch.S., O.H.F., A.D., M.A.I.), Internal Medicine (A.G.U.), Radiology (M.A.I.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Sedaghat
authors.affiliation: Departments of Epidemiology (S.S., R.P., A.G.U., A.H., B.H.Ch.S., O.H.F., A.D., M.A.I.), Internal Medicine (A.G.U.), Radiology (M.A.I.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Raha
authors.initials: R
authors.lastname: Pazoki
authors.affiliation: Departments of Epidemiology (S.S., R.P., A.G.U., A.H., B.H.Ch.S., O.H.F., A.D., M.A.I.), Internal Medicine (A.G.U.), Radiology (M.A.I.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Departments of Epidemiology (S.S., R.P., A.G.U., A.H., B.H.Ch.S., O.H.F., A.D., M.A.I.), Internal Medicine (A.G.U.), Radiology (M.A.I.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Departments of Epidemiology (S.S., R.P., A.G.U., A.H., B.H.Ch.S., O.H.F., A.D., M.A.I.), Internal Medicine (A.G.U.), Radiology (M.A.I.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Bruno H Ch
authors.initials: BH
authors.lastname: Stricker
authors.affiliation: Departments of Epidemiology (S.S., R.P., A.G.U., A.H., B.H.Ch.S., O.H.F., A.D., M.A.I.), Internal Medicine (A.G.U.), Radiology (M.A.I.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Departments of Epidemiology (S.S., R.P., A.G.U., A.H., B.H.Ch.S., O.H.F., A.D., M.A.I.), Internal Medicine (A.G.U.), Radiology (M.A.I.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: Departments of Epidemiology (S.S., R.P., A.G.U., A.H., B.H.Ch.S., O.H.F., A.D., M.A.I.), Internal Medicine (A.G.U.), Radiology (M.A.I.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D015331:Cohort Studies; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011446:Prospective Studies; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood
chemical_list: D000959:Antihypertensive Agents; D004232:Diuretics; D014527:Uric Acid
keywords: blood pressure; diuretics; genetic pleiotropy; uric acid