Journal
BEST PRACTICE & RESEARCH CLINICAL OBSTETRICS & GYNAECOLOGY
Volume 52, Issue -, Pages 33-47Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.bpobgyn.2018.05.003
Keywords
Gestational duration; Preterm birth; Complex human trait; Genome-wide association
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Funding
- March of Dimes
- National Institutes of Health
- Fifth Third Foundation
- Bill and Melinda Gates Foundation
- Burroughs Wellcome Fund
- Cincinnati Children's Hospital Medical Center
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The fine control of birth timing is important to human survival and evolution. A key challenge in studying the mechanisms underlying the regulation of human birth timing is that human parturition is a unique to human event animal models provide only limited information. The duration of gestation or the risk of preterm birth is a complex human trait under genetic control from both maternal and fetal genomes. Genomic discoveries through genome-wide association (GWA) studies would implicate relevant genes and pathways. Similar to other complex human traits, gestational duration is likely to be influenced by numerous genetic variants of small effect size. The detection of these small-effect genetic variants requires very large sample sizes. In addition, several practical and analytical challenges, in particular the involvement of both maternal and fetal genomes, further complicate the genetic studies of gestational duration and other pregnancy phenotypes. Despite these challenges, large-scale GWA studies have already identified several genomic loci associated with gestational duration or the risk of preterm birth. These genomic discoveries have revealed novel insights about the biology of human birth timing. Expanding genomic discoveries in larger datasets by more refined analytical approaches, together with the functional analysis of the identified genomic loci, will collectively elucidate the biological processes underlying the control of human birth timing. (C) 2018 The Authors. Published by Elsevier Ltd.
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