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: 3.97). 08/2008; 199(1):43.e1-5. DOI: 10.1016/j.ajog.2007.12.014
Source: PubMed

ABSTRACT 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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    • "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.
    Environment International 12/2014; 73:143–149. DOI:10.1016/j.envint.2014.07.014 · 5.66 Impact Factor
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    • "Women delivering preterm are at increased risk of preterm birth in the subsequent pregnancies, reflecting the effects of environment/genetics or both. Although environmental factors are important (Longnecker et al., 2001; Pathak et al., 2009), genetics clearly plays a role, with heritability recently estimated as 34% for birth timing (Kistka et al., 2008). Identification of genetic susceptibility variants will lead to a better understanding of the role of variable factors in PTD. "
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    ABSTRACT: We investigated the association between glutathione S-transferases mu1 (GSTM1), theta 1 (GSTT1), Cytochrome P450IA1-T6235C (rs4646903, CYP1A1m1) and CYP1A1-1462V (rs1048943, CYP1A1m2) gene polymorphisms, and organochlorine pesticides (OCPs) level with risk of preterm delivery (PTD). Maternal and cord blood samples of PTD (n = 156) cases and subjects of full-term delivery (FTD, n = 151) were collected at the time of delivery/after delivery. Women occupationally exposed to OCPs and other high-risk factors such as anemia, hypertension and dietary habit were excluded. The OCP levels were estimated by gas chromatography, and polymorphic analysis of GSTM1/GSTT1 and CYP450 genes was carried out using multiplex PCR and PCR-restriction fragment length polymorphism, respectively. The frequency of GSTM1/GSTT1 (null) genotype was significantly higher in PTD cases than in the controls. Significantly high levels of α-hexachlorocyclohexane (HCH), γ-HCH and Dichlorodiphenyldichloroethylene (p'p'-DDE) were observed in maternal blood, while significantly high levels of p,p'-dichlorodiphenyltrichloroethane and p'p'-DDE were found in the cord blood of PTD cases compared with the controls. A significant association was seen between β-HCH and GSTM1 genotype when interaction between GSTM1 gene polymorphism, maternal blood OCP levels and period of gestation (POG) was ascertained. A significant reduction in POG was observed. Similarly, cord blood dieldrin levels were significantly associated with CYP1A1m2 (Aa/aa) with reduction in POG. Our observations indicate that higher levels of OCPs in pregnant women may be associated with increased risk of 'idiopathic' PTD. Furthermore, this study shows that the interaction between high OCPs levels and polymorphism in CYP1A1m2 and GSTM1 null genotypes may magnify the risk of PTD, thus providing evidence for a gene-environment interaction in pregnant women
    Molecular Human Reproduction 01/2013; 19(1):35-42. · 3.48 Impact Factor
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    • "The lack of strong support for a fetal genetic effect in this study and absence in others (Kistka et al., 2008) is curious since birth timing has been described as a culmination of series of physiologic and anatomic changes in both mother and fetus (Chaudhari et al., 2008; Lye et al., 2007). Indeed, genetic disorders affecting the fetus including certain forms of Ehlers-Danlos syndrome are known to predispose to early birth resulting from preterm premature rupture of the fetal membranes (PPROM), whereas Ehlers-Danlos syndrome in the mother with an unaffected fetus does not predispose to preterm birth (Anum, Hill et al., 2009). "
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    ABSTRACT: The analysis of genetic and environmental contributions to preterm birth is not straightforward in family studies, as etiology could involve both maternal and fetal genes. Markov Chain Monte Carlo (MCMC) methods are presented as a flexible approach for defining user-specified covariance structures to handle multiple random effects and hierarchical dependencies inherent in children of twin (COT) studies of pregnancy outcomes. The proposed method is easily modified to allow for the study of gestational age as a continuous trait and as a binary outcome reflecting the presence or absence of preterm birth. Estimation of fetal and maternal genetic factors and the effect of the environment are demonstrated using MCMC methods implemented in WinBUGS and maximum likelihood methods in a Virginia COT sample comprising 7,061 births. In summary, although the contribution of maternal and fetal genetic factors was supported using both outcomes, additional births and/or extended relationships are required to precisely estimate both genetic effects simultaneously. We anticipate the flexibility of MCMC methods to handle increasingly complex models to be of particular relevance for the study of birth outcomes.
    Twin Research and Human Genetics 09/2009; 12(4):333-42. DOI:10.1375/twin.12.4.333 · 1.92 Impact Factor
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