title: OS050. Genetic variants in pre-eclampsia: a meta-analysis.
abstract: BACKGROUND
  Preeclampsia has a clear familial component, suggesting that the syndrome may be partly attributable to genetic susceptibility. The search for susceptibility genes has lead to a massive increase in the number of published studies involving genetic associations in preeclampsia. However, attempts to replicate these findings have yielded inconsistent results. This meta-analysis aims to assess the pooled effect of each genetic variant that is reproducibly associated with preeclampsia.
  
  
  OBJECTIVE
  To create an overview of the genetic variants that are reproducibly associated with preeclampsia.
  
  
  METHODS
  Studies assessing the association between genes and preeclampsia were searched in PubMed, EMBASE and Web of Science. We selected all genetic variants that were significantly associated with preeclampsia in an initial study and then independently reproduced in at least one additional study. Subsequently, all studies assessing these reproduced variants were included. The association between these variants and preeclampsia was calculated at the allele level and the main measure of effect was a pooled odds ratio.
  
  
  RESULTS
  The literature search resulted in 2965 citations, of which 542 were genetic association studies investigating preeclampsia. We identified 23 replicated genetic variants, of which 8 remained significantly associated with preeclampsia in a random-effects meta-analysis. These variants were in or near the following genes: ACE,AGT,CTLA4,F2,FV (two variants),LPL and SERPINE1.
  
  
  CONCLUSIONS
  This meta-analysis found 8 genetic variants associated with preeclampsia. Most of these variants are in the renin-angiotensin and the coagulation system. Importantly, many of the variants that were associated with preeclampsia are known to be risk factors for the development of cardiovascular disease, indicating that preeclampsia and cardiovascular disease have shared genetic risk factors. The relative contribution and relevance of the identified genes in the pathogenesis of preeclampsia should be the focus of future studies.
authors.affiliation: Pathology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Buurma
authors.affiliation: Pathology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Turner
authors.affiliation: Medical Statistics and and Bioinformatics, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Driessen
authors.affiliation: Pathology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Mooyaart
authors.affiliation: Walaeus Library, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Schoones
authors.affiliation: Pathology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Bruijn
authors.affiliation: Obstetrics, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Bloemenkamp
authors.affiliation: Pathology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Baelde