title: Genetic Predisposition to Dyslipidemia and Risk of Preeclampsia.
abstract: BACKGROUND
  Large epidemiologic studies support the role of dyslipidemia in preeclampsia; however, the etiology of preeclampsia or whether dyslipidemia plays a causal role remains unclear. We examined the association between the genetic predisposition to dyslipidemia and risk of preeclampsia using validated genetic markers of dyslipidemia.
  
  
  METHODS
  Preeclampsia cases (n = 164) and normotensive controls (n = 110) were selected from live birth certificates to nulliparous Iowa women during the period August 2002 to May 2005. Disease status was verified by medical chart review. Genetic predisposition to dyslipidemia was estimated by 4 genetic risk scores (GRS) (total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides) on the basis of established loci for blood lipids. Logistic regression analyses were used to evaluate the relationships between each of the 4 genotype scores and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry.
  
  
  RESULTS
  The GRS related to higher levels of TC, LDL-C, and triglycerides demonstrated no association with the risk of preeclampsia in either the Iowa or replication population. The GRS related to lower HDL-C was marginally associated with an increased risk for preeclampsia (odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.99-1.07; P = 0.10). In the independent replication population, the association with the HDL-C GRS was also marginally significant (OR = 1.03, 95% CI: 1.00-1.06; P = 0.04).
  
  
  CONCLUSIONS
  Our data suggest a potential effect between the genetic predisposition to dyslipidemic levels of HDL-C and an increased risk of preeclampsia, and, as such, suggest that dyslipidemia may be a component along the causal pathway to preeclampsia.
authors.affiliation: Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa, USA; Present address: 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, University of Iowa College of Public Health, Iowa City, Iowa, USA;
authors.forename: Audrey F
authors.initials: AF
authors.lastname: Saftlas
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: Division 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, University of Iowa College of Public Health, 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, University of Iowa College of Public Health, Iowa City, Iowa, USA; kelli-ryckman@uiowa.edu.
authors.forename: Kelli K
authors.initials: KK
authors.lastname: Ryckman
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D050171:Dyslipidemias / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007484:Iowa; D016015:Logistic Models; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D011247:Pregnancy; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides
keywords: blood pressure; dyslipidemia; genetic epidemiology; genetic risk score; hypertension; preeclampsia.