title: Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia.
abstract: BACKGROUND
  Preeclampsia is a hypertensive complication of pregnancy characterized by novel onset of hypertension after 20 weeks gestation, accompanied by proteinuria. Epidemiological evidence suggests that genetic susceptibility exists for preeclampsia; however, whether preeclampsia is the result of underlying genetic risk for essential hypertension has yet to be investigated. Based on the hypertensive state that is characteristic of preeclampsia, we aimed to determine if established genetic risk scores (GRSs) for hypertension and blood pressure are associated with preeclampsia.
  
  
  METHODS
  Subjects consisted of 162 preeclamptic cases and 108 normotensive pregnant controls, all of Iowa residence. Subjects' DNA was extracted from buccal swab samples and genotyped on the Affymetrix Genome-wide Human SNP Array 6.0 (Affymetrix, Santa Clara, CA). Missing genotypes were imputed using MaCH and Minimac software. GRSs were calculated for hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) using established genetic risk loci for each outcome. Regression analyses were performed to determine the association between GRS and risk of preeclampsia. These analyses were replicated in an independent US population of 516 cases and 1,097 controls of European ancestry.
  
  
  RESULTS
  GRSs for hypertension, SBP, DBP, and MAP were not significantly associated with risk for preeclampsia (P > 0.189). The results of the replication analysis also yielded nonsignificant associations.
  
  
  CONCLUSIONS
  GRSs for hypertension and blood pressure are not associated with preeclampsia, suggesting that an underlying predisposition to essential hypertension is not on the causal pathway of preeclampsia.
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA;
authors.forename: Caitlin J
authors.initials: CJ
authors.lastname: Smith
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA;
authors.forename: Audrey F
authors.initials: AF
authors.lastname: Saftlas
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA; Department of Genetics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA;
authors.forename: Cassandra N
authors.initials: CN
authors.lastname: Spracklen
authors.affiliation: Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island, USA;
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Triche
authors.affiliation: Center for Human Genetic Research and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA;
authors.forename: Andrew
authors.initials: A
authors.lastname: Bjonnes
authors.affiliation: Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA;
authors.forename: Brendan
authors.initials: B
authors.lastname: Keating
authors.affiliation: Center for Human Genetic Research and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA;
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
authors.affiliation: Department of Biostatistics, University of Iowa College of Public Health, Iowa City, Iowa, USA;
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Breheny
authors.affiliation: Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA;
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Dewan
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA;
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Robinson
authors.affiliation: Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA.
authors.forename: Josephine
authors.initials: J
authors.lastname: Hoh
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA; kelli-ryckman@uiowa.edu.
authors.forename: Kelli K
authors.initials: KK
authors.lastname: Ryckman
mesh_terms: D001794:Blood Pressure / Q000502:physiology*; D001795:Blood Pressure Determination; D000075222:Essential Hypertension; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000453:epidemiology / Q000503:physiopathology; D015994:Incidence; D011225:Pre-Eclampsia / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D011247:Pregnancy; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology
keywords: blood pressure; genetic epidemiology; genetic predisposition to disease; hypertension; maternal; preeclampsia; pregnancy.