Abstract
Preterm birth (PTB), defined as birth prior to a gestational age (GA) of 37 completed weeks, affects more than 10 % of births worldwide. PTB is the leading cause of neonatal mortality and is associated with a broad spectrum of lifelong morbidity in survivors. The etiology of spontaneous PTB (SPTB) is complex and has an important genetic component. Previous studies have compared monozygotic and dizygotic twin mothers and their families to estimate the heritability of SPTB, but these approaches cannot separate the relative contributions of the maternal and the fetal genomes to GA or SPTB. Using the Utah Population Database, we assessed the heritability of GA in more than 2 million post-1945 Utah births, the largest familial GA dataset ever assembled. We estimated a narrow-sense heritability of 13.3 % for GA and a broad-sense heritability of 24.5 %. A maternal effect (which includes the effect of the maternal genome) accounts for 15.2 % of the variance of GA, and the remaining 60.3 % is contributed by individual environmental effects. Given the relatively low heritability of GA and SPTB in the general population, multiplex SPTB pedigrees are likely to provide more power for gene detection than will samples of unrelated individuals. Furthermore, nongenetic factors provide important targets for therapeutic intervention.
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Acknowledgments
EASC is supported by National Institutes of Health, National Institute of Child Health and Human Development (K23HD061910). This investigation was supported by the University of Utah Study Design and Biostatistics Center, with funding in part from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 8UL1TR000105 (formerly UL1RR025764). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are grateful to the Utah Population Database (UPDB) for providing and maintaining invaluable data for quantitative genetics analysis. We would also like to thank Jahn Barlow from the Utah Resource for Genetic and Epidemiologic Research (RGE), and Kristine Larrabee from the Department of Obstetrics and Gynecology, University of Utah, for their help and support for this study.
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Wu, W., Witherspoon, D.J., Fraser, A. et al. The heritability of gestational age in a two-million member cohort: implications for spontaneous preterm birth. Hum Genet 134, 803–808 (2015). https://doi.org/10.1007/s00439-015-1558-1
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DOI: https://doi.org/10.1007/s00439-015-1558-1