Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Timing of Group B Streptococcus Screening in Pregnancy: A Systematic Review

Background: Group B streptococcus (GBS) is an important cause of neonatal sepsis. Guidelines advise to collect cultures at 35-37 weeks' gestation and to administer intrapartum antibiotic prophylaxis in case of GBS-positive cultures, as well as in all preterm deliveries. Improved effectiveness of antenatal cultures might help to further decrease GBS early-onset disease. Objective: To determine the best timing of antenatal cultures, which may help establish optimal prevention of perinatal GBS infection in both term and preterm neonates. Methods: PubMed and EMBASE databases were searched for relevant articles published from 1966 to February 2009. Nine articles were included. Information about study features and predictive values of antenatal cultures were abstracted. Results: Positive predictive values for antenatal GBS cultures ranged from 43 to 100% (mean 69%) and negative predictive values from 80 to 100% (mean 94%). GBS cultures collected in late pregnancy had high positive predictive values for colonization during delivery. The negative predictive value was high and relatively constant regardless of GA. Conclusions: This systematic review confirms recommendations to screen pregnant women for colonization of GBS at 35-37 weeks' gestation, but one should be aware of the limitations of screening, with 6% of GBS carriers remaining undetected in antenatal cultures. Copyright (C) 2009 S. Karger AG, BaselClinical epidemiolog