Familial aggregation of preeclampsia and intrauterine growth restriction in a genetically isolated population in The Netherlands

Eur J Hum Genet. 2008 Dec;16(12):1437-42. doi: 10.1038/ejhg.2008.118. Epub 2008 Jul 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Consanguinity
  • Family Characteristics
  • Family*
  • Female
  • Fetal Growth Retardation / epidemiology
  • Fetal Growth Retardation / genetics*
  • Founder Effect
  • Humans
  • Incidence
  • Netherlands / epidemiology
  • Pre-Eclampsia / epidemiology
  • Pre-Eclampsia / genetics*
  • Pregnancy
  • Social Isolation*