title: Refined phenotyping identifies links between preeclampsia and related diseases in a Norwegian preeclampsia family cohort.
abstract: OBJECTIVE
  Preeclampsia is a complex genetic disease of pregnancy with a heterogenous presentation, unknown cause and potential severe outcomes for both mother and child. Preeclamptic women have increased risk for atherothrombotic cardiovascular disease. We aimed to identify heritabilities and phenotypic correlations of preeclampsia and related conditions in the Norwegian Preeclampsia Family Biobank.
  
  
  METHODS
  By applying a variance components model, a total of 493 individuals (from 138 families with increased occurrence of preeclampsia) were classified according to 30 disease-related phenotypes.
  
  
  RESULTS
  Of parous women, 75.7% (263/338) had experienced preeclampsia and 35.7% of women with and 22.4% without preeclampsia delivered children small for gestational age (SGA). We identified 11 phenotypes as heritable. The increased occurrence of preeclampsia was reflected by the presence [heritability (H2r) = 0.60)] and severity (H2r = 0.15) of preeclampsia and being born in a preeclamptic pregnancy (H2r = 0.25). Other heritable phenotypes identified included SGA (H2r = 0.40), chronic hypertension (H2r = 0.57), severity of atherothrombotic cardiovascular disease (H2r = 0.31), BMI (H2r = 0.60) and pulmonary disease (H2r = 0.91). The heritable phenotype preeclampsia overlapped with SGA (P = 0.03), whereas pulmonary disease was phenotypically correlated with atherothrombotic cardiovascular disease (P < 0.01), SGA (P = 0.02) and BMI (P = 0.02).
  
  
  CONCLUSIONS
  This is the first study identifying the H2r of a range of health-related conditions in preeclamptic families. Our study demonstrates how refinement of phenotypes leads to better H2r estimation and the identification of a biological relationship between preeclampsia and related traits.
authors.affiliation: aDepartment of Gynecology and Obstetrics, Haukeland University Hospital bDepartment of Clinical Science, University of Bergen, Bergen, Norway cCentre for Genetic Origins of Health and Disease, University of Western Australia, Perth, Australia dCentre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim eDepartment of Obstetrics and Gynecology, Stavanger University Hospital, Stavanger fDepartment of Cancer Research and Molecular Medicine gDepartment of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim hDepartment of Heart Disease, Haukeland University Hospital, Bergen, Norway.
authors.forename: Liv Cecilie V
authors.initials: LC
authors.lastname: Thomsen
authors.forename: Phillip E
authors.initials: PE
authors.lastname: Melton
authors.forename: Kjersti
authors.initials: K
authors.lastname: Tollaksen
authors.forename: Ingvill
authors.initials: I
authors.lastname: Lyslo
authors.forename: Linda T
authors.initials: LT
authors.lastname: Roten
authors.forename: Maria L
authors.initials: ML
authors.lastname: Odland
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Strand
authors.forename: Ottar
authors.initials: O
authors.lastname: Nygård
authors.forename: Chen
authors.initials: C
authors.lastname: Sun
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Iversen
authors.forename: Rigmor
authors.initials: R
authors.lastname: Austgulen
authors.forename: Eric K
authors.initials: EK
authors.lastname: Moses
authors.forename: Line
authors.initials: L
authors.lastname: Bjørge
mesh_terms: D000328:Adult; D018070:Biological Specimen Banks; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D009035:Mothers; D009664:Norway; D010641:Phenotype; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy