title: Cardiovascular consequences of a polygenetic component of blood pressure in an urban-based longitudinal study: the Malmö diet and cancer.
abstract: BACKGROUND
  A recently published genome wide association study identified 29 single nucleotide polymorphisms (SNPs) influencing blood pressure (BP). Case-control studies suggest that a genetic risk score (GRS) based on these 29 SNPs affect the risk of cardiovascular disease (CVD), but its role for CVD at population level is unknown. Here, we prospectively evaluate the impact of this polygenetic BP component on CVD morbidity and mortality in a large urban-based middle-aged population.
  
  
  METHODS
  The 29 previously BP associated SNPs were genotyped in the Swedish Malmö Diet and Cancer Study; (n = 27,003 with at least 24 valid SNPs). The number of BP elevating alleles of each SNPs, weighted by their effect size in the discovery studies, was summed into a BP-GRS.
  
  
  RESULTS
  Using regression models, we found significant associations of the BP-GRS, cross-sectionally, with BP and hypertension prevalence, prospectively, with incident cardiovascular morbidity and mortality during 14.2 ± 3.2 years of follow-up. After adjustment for traditional cardiovascular risk factors (TRF), including hypertension, the BP-GRS remained significantly associated only with CVDs [in terms of strokes and coronary artery disease; hazard ratio 1.15; 95% confidence interval (CI) 1.06-1.24 comparing the third vs. first tertile; P = 0.003]. Calibration, discrimination and reclassification analyses did not show a meaningful increment in prediction using the BP-GRS in addition to the model encompassing only the TRF.
  
  
  CONCLUSIONS
  The polygenetic component of BP influences risk of cardiovascular morbidity and mortality. However, the effect size is small and unlikely to be useful for prediction at the population level.
authors.affiliation: aDepartment of Clinical Sciences, Lund University, University Hospital of Malmö, Malmö, Sweden bDepartment of Medicine, University Hospital of Verona, Verona, Italy *Cristiano Fava and Therese Ohlsson contributed equally to the to the writing of this article.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Fava
authors.forename: Therese
authors.initials: T
authors.lastname: Ohlsson
authors.forename: Marketa
authors.initials: M
authors.lastname: Sjögren
authors.forename: Angela
authors.initials: A
authors.lastname: Tagetti
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: Pietro
authors.initials: P
authors.lastname: Minuz
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D015331:Cohort Studies; D004032:Diet; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D014505:Urban Population