Heritability of parturition timing: an extended twin design analysis

Department of Pediatrics, Washington University, St Louis, MO, USA.
American journal of obstetrics and gynecology (Impact Factor: 4.7). 08/2008; 199(1):43.e1-5. DOI: 10.1016/j.ajog.2007.12.014
Source: PubMed


The objective of the study was to assess relative maternal and paternal genetic influences on birth timing.
Utilizing The Netherlands Twin Registry, we examined the correlation in birth timing of infants born to monozygotic (MZ) twins and their first-degree relatives (dizygotic twins and siblings of twins). Genetic models estimated the relative influence of genetic and common environmental factors through model fitting of additive genetic (A), common environmental (C), individual-specific environmental factors, and combinations thereof.
We evaluated birth timing correlation among the infants of 1390 twins and their 644 siblings. The correlation in MZ female twins (r = 0.330) was greater than MZ male twins (r = -0.096). Positive correlation were also found in sister-sister pairs (r = 0.223) but not in brother-brother (r = -0.045) or brother-sister pairs (r = -0.038). The most parsimonious AE model indicated a significant maternal contribution of genetic and individual-specific environmental factors to birth timing, but no paternal heritability was demonstrated. Heritability of birth timing in women was 34%; and the remaining variance (66%) was caused by individual-specific environmental factors.
Our data implicate a significant contribution of maternal but not paternal genetic influences on birth timing.

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    • "Substantial evidence has accumulated that genetic factors, largely residing in the maternal genome, contribute up to 40% of the variation in birth timing and preterm birth. This evidence includes epidemiological data, analysis of birth timing to twins, and segregation analysis of pedigrees (Clausson et al. 2000; Kistka et al. 2008; Boyd et al. 2009; Plunkett et al. 2009). Moreover, with sequenced genomes now available for at least two dozen mammals at high coverage, and another dozen or more at lower coverage, the opportunity exists to use comparative genomic strategies to reveal genes and pathways that have been shaped through evolution to result in the current patterns of human and other mammal reproductive strategies and mechanisms. "
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    ABSTRACT: The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
    Full-text · Article · Feb 2015 · Cold Spring Harbor Perspectives in Medicine
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    • "Internationally, although some studies have reported associations between PM 2.5 exposure and PTB (Brook et al., 2010; Dellinger et al., 2001; Pereira et al., 2014; Sørensen et al., 2003; van Eeden et al., 2005), evidence for a consistent association remains elusive. It is uncertain whether the results of past studies were affected by individual predisposition (Goldenberg et al., 2008; Kistka et al., 2008) that might vary considerably between women. In Australia, the preterm rate can be as high as 19%–36% in Aboriginal communities (Bar-Zeev et al., 2012). "
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    ABSTRACT: Objective A recent longitudinal study reported an association between fine particulate (PM2.5) exposure and preterm birth (PTB) in a US cohort. We applied the same design to an Australian cohort to investigate associations with PTB and pre-labor rupture of membranes (PROM). Methods From 287,680 births, we selected 39,189 women who had singleton births at least twice in Western Australia in 1997–2007 (n = 86,844 births). Analyses matched pregnancies to the same women with conditional logistic regression. Results For PROM adjusted odds ratios (ORs) for a 1 μg/m3 increase in PM2.5 in the first trimester, second trimester, third trimester, and whole pregnancy were 1.00 (95% confidence interval (CI): 0.97, 1.03), 1.03 (95% CI: 1.00, 1.06), 1.02 (95% CI: 1.00, 1.05), and 1.02 (95% CI: 0.99, 1.05) respectively. For PTB, corresponding ORs were 1.00 (95% CI: 0.96, 1.04), 1.00 (95% CI: 0.96, 1.04), 0.98 (95% CI: 0.94, 1.02), and 0.99 (95% CI: 0.95, 1.04) respectively. Conclusion Risk of PROM was greater for pregnancies with elevated PM2.5 exposure in the second trimester than were other pregnancies to the same Australian women at lower exposure. There was insufficient evidence for an association with PTB, indicating that a longer time period might be needed to observe an association if a causal effect exists.
    Full-text · Article · Dec 2014 · Environment International
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    • "Birth before 37 weeks of gestation increases a woman's own risk of preterm delivery by almost 20% [11], and having a previous preterm delivery confers an increased risk of recurrent preterm delivery [13]. Although the paternal contribution to birth timing in the context of fetal genetic influences has been somewhat controversial, data suggest a smaller role for paternal compared with maternal fetal genes in birth timing [36,37]. "
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    ABSTRACT: Preterm birth (delivery at less than 37 weeks of gestation) is the leading cause of infant mortality worldwide. So far, the application of animal models to understand human birth timing has not substantially revealed mechanisms that could be used to prevent prematurity. However, with amassing data implicating an important role for genetics in the timing of the onset of human labor, the use of modern genomic approaches, such as genome-wide association studies, rare variant analyses using whole-exome or genome sequencing, and family-based designs, holds enormous potential. Although some progress has been made in the search for causative genes and variants associated with preterm birth, the major genetic determinants remain to be identified. Here, we review insights from and limitations of animal models for understanding the physiology of parturition, recent human genetic and genomic studies to identify genes involved in preterm birth, and emerging areas that are likely to be informative in future investigations. Further advances in understanding fundamental mechanisms, and the development of preventative measures, will depend upon the acquisition of greater numbers of carefully phenotyped pregnancies, large-scale informatics approaches combining genomic information with information on environmental exposures, and new conceptual models for studying the interaction between the maternal and fetal genomes to personalize therapies for mothers and infants. Information emerging from these advances will help us to identify new biomarkers for earlier detection of preterm labor, develop more effective therapeutic agents, and/or promote prophylactic measures even before conception.
    Full-text · Article · Apr 2013 · Genome Medicine
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