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Targeted Sequencing and Meta-Analysis of Preterm Birth

Understanding the genetic contribution(s) to the risk of preterm birth may lead to the development of interventions for treatment, prediction and prevention. Twin studies suggest heritability of preterm birth is 36–40%. Large epidemiological analyses support a primary maternal origin for recurrence...

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Autores principales: Uzun, Alper, Schuster, Jessica, McGonnigal, Bethany, Schorl, Christoph, Dewan, Andrew, Padbury, James
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862658/
https://www.ncbi.nlm.nih.gov/pubmed/27163930
http://dx.doi.org/10.1371/journal.pone.0155021
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author Uzun, Alper
Schuster, Jessica
McGonnigal, Bethany
Schorl, Christoph
Dewan, Andrew
Padbury, James
author_facet Uzun, Alper
Schuster, Jessica
McGonnigal, Bethany
Schorl, Christoph
Dewan, Andrew
Padbury, James
author_sort Uzun, Alper
collection PubMed
description Understanding the genetic contribution(s) to the risk of preterm birth may lead to the development of interventions for treatment, prediction and prevention. Twin studies suggest heritability of preterm birth is 36–40%. Large epidemiological analyses support a primary maternal origin for recurrence of preterm birth, with little effect of paternal or fetal genetic factors. We exploited an “extreme phenotype” of preterm birth to leverage the likelihood of genetic discovery. We compared variants identified by targeted sequencing of women with 2–3 generations of preterm birth with term controls without history of preterm birth. We used a meta-genomic, bi-clustering algorithm to identify gene sets coordinately associated with preterm birth. We identified 33 genes including 217 variants from 5 modules that were significantly different between cases and controls. The most frequently identified and connected genes in the exome library were IGF1, ATM and IQGAP2. Likewise, SOS1, RAF1 and AKT3 were most frequent in the haplotype library. Additionally, SERPINB8, AZU1 and WASF3 showed significant differences in abundance of variants in the univariate comparison of cases and controls. The biological processes impacted by these gene sets included: cell motility, migration and locomotion; response to glucocorticoid stimulus; signal transduction; metabolic regulation and control of apoptosis.
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spelling pubmed-48626582016-05-18 Targeted Sequencing and Meta-Analysis of Preterm Birth Uzun, Alper Schuster, Jessica McGonnigal, Bethany Schorl, Christoph Dewan, Andrew Padbury, James PLoS One Research Article Understanding the genetic contribution(s) to the risk of preterm birth may lead to the development of interventions for treatment, prediction and prevention. Twin studies suggest heritability of preterm birth is 36–40%. Large epidemiological analyses support a primary maternal origin for recurrence of preterm birth, with little effect of paternal or fetal genetic factors. We exploited an “extreme phenotype” of preterm birth to leverage the likelihood of genetic discovery. We compared variants identified by targeted sequencing of women with 2–3 generations of preterm birth with term controls without history of preterm birth. We used a meta-genomic, bi-clustering algorithm to identify gene sets coordinately associated with preterm birth. We identified 33 genes including 217 variants from 5 modules that were significantly different between cases and controls. The most frequently identified and connected genes in the exome library were IGF1, ATM and IQGAP2. Likewise, SOS1, RAF1 and AKT3 were most frequent in the haplotype library. Additionally, SERPINB8, AZU1 and WASF3 showed significant differences in abundance of variants in the univariate comparison of cases and controls. The biological processes impacted by these gene sets included: cell motility, migration and locomotion; response to glucocorticoid stimulus; signal transduction; metabolic regulation and control of apoptosis. Public Library of Science 2016-05-10 /pmc/articles/PMC4862658/ /pubmed/27163930 http://dx.doi.org/10.1371/journal.pone.0155021 Text en © 2016 Uzun et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Uzun, Alper
Schuster, Jessica
McGonnigal, Bethany
Schorl, Christoph
Dewan, Andrew
Padbury, James
Targeted Sequencing and Meta-Analysis of Preterm Birth
title Targeted Sequencing and Meta-Analysis of Preterm Birth
title_full Targeted Sequencing and Meta-Analysis of Preterm Birth
title_fullStr Targeted Sequencing and Meta-Analysis of Preterm Birth
title_full_unstemmed Targeted Sequencing and Meta-Analysis of Preterm Birth
title_short Targeted Sequencing and Meta-Analysis of Preterm Birth
title_sort targeted sequencing and meta-analysis of preterm birth
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862658/
https://www.ncbi.nlm.nih.gov/pubmed/27163930
http://dx.doi.org/10.1371/journal.pone.0155021
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