title: Familial aggregation of preeclampsia and intrauterine growth restriction in a genetically isolated population in The Netherlands.
abstract: Preeclampsia and intrauterine growth restriction are related, pregnancy-specific disorders with a substantial genetic influence, which may have a joint genetic aetiology. We investigated familial aggregation, consanguinity and parent-of-origin effects for preeclampsia and IUGR. Fifty women with previous preeclampsia and 56 with previous pregnancies complicated by intrauterine growth restriction were recruited from a recent genetically isolated population in the Netherlands. Their relationships were estimated by means of a large genealogy database that contains information on more than 110 000 individuals from the isolate over 23 generations. Relationships were quantified using kinship and inbreeding coefficients. Parent-of-origin effects were evaluated by comparing parental kinships. Eighty-six women (39 preeclampsia and 47 intrauterine growth restriction) could be linked to one common ancestor within 14 generations. The proportion of related women with previous preeclampsia (95.6%) or pregnancies complicated by intrauterine growth restriction (95.1%) was significantly greater than expected by chance (P<0.001). Combined analysis of both disorders did not change the magnitude of familial aggregation. The proportion of women born from consanguineous marriages was increased in women with previous preeclampsia (81.8%) and those with intrauterine growth restriction (78%) compared to a random sample (P<0.001). Maternal and paternal kinships were not significantly different in both disorders. We demonstrate cosegregation of preeclampsia and intrauterine growth restriction, supporting a common genetic aetiology. The high proportion of parental consanguineous marriages suggests the possibility of an underlying recessive mutation. No evidence was found for a parent-of-origin effect either in preeclampsia or in intrauterine growth restriction.
authors.affiliation: Department of Obstetrics and Gynaecology, Division of Obstetrics and Prenatal Medicine, University Medical Centre Rotterdam, The Netherlands. a.berends@erasmusmc.nl
authors.forename: Anne L
authors.initials: AL
authors.lastname: Berends
authors.forename: Eric A
authors.initials: EA
authors.lastname: Steegers
authors.forename: Aaron
authors.initials: A
authors.lastname: Isaacs
authors.forename: Y S
authors.initials: YS
authors.lastname: Aulchenko
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.forename: Christianne J
authors.initials: CJ
authors.lastname: de Groot
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003241:Consanguinity; D005190:Family; D005191:Family Characteristics; D005260:Female; D005317:Fetal Growth Retardation / Q000453:epidemiology / Q000235:genetics*; D018703:Founder Effect; D006801:Humans; D015994:Incidence; D009426:Netherlands / Q000453:epidemiology; D011225:Pre-Eclampsia / Q000453:epidemiology / Q000235:genetics*; D011247:Pregnancy; D012934:Social Isolation