Maternal and fetal genetic factors account for most of familial aggregation of preeclampsia: A population‐based Swedish cohort study

There is accumulated evidence for genetic influences on preeclampsia. However, no study has been able to separate the effects of maternal and fetal genetic factors from environmental factors, and there are still uncertainties about the origin and magnitude of the genetic effects. We used the population-based Swedish Birth and Multi-Generation Registries to identify a cohort of women who gave birth from 1987 through 1997. In order to separate the genetic and environmental contributions to preeclampsia, we analyzed pregnancy outcomes from families joined by full siblings. We included information from 244,564 sibling pairs (62,236 sister pairs, 63,288 brother pairs, and 119,040 sister-brother pairs), who had 701,488 pregnancies. We found that 35% of the variance in liability of preeclampsia was attributable to maternal genetic effects, 20% to fetal genetic effects (with similar contribution of maternal and paternal genetic effects), 13% to the couple effect, less than 1% to shared sibling environment, and 32% to unmeasured factors. Among women and men without a history of preeclampsia, partner change reduced the risk of preeclampsia (odds ratio, 0.6; 95 percent confidence interval, 0.4-0.9). Genetic factors account for more than half of the liability of preeclampsia, and maternal genes contribute more than fetal genes. We suggest that the couple effect is due to a genetic interaction between mother and father.