Targeted Sequencing and Meta-Analysis of Preterm Birth

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 May 11

PMID 27163930

Citations 11

Authors

Alper Uzun

Jessica Schuster

Bethany McGonnigal

Christoph Schorl

Andrew DeWan

James Padbury

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

A genome-wide and candidate gene association study of preterm birth in Korean pregnant women.

Hur Y, Yoo J, You Y, Park S, Kim S, Lee G PLoS One. 2023; 18(11):e0294948.

PMID: 38019868 PMC: 10686439. DOI: 10.1371/journal.pone.0294948.

Gene Expression Behavior of a Set of Genes in Platelet and Tissue Samples from Patients with Breast Cancer.

Burciaga-Hernandez L, Cueto-Villalobos C, Ortega-Pinon N, Gonzalez-Curiel I, Godina-Gonzalez S, Mendez-Frausto G Int J Mol Sci. 2023; 24(9).

PMID: 37176055 PMC: 10179257. DOI: 10.3390/ijms24098348.

Genetics, epigenetics, and transcriptomics of preterm birth.

Jain V, Monangi N, Zhang G, Muglia L Am J Reprod Immunol. 2022; 88(4):e13600.

PMID: 35818963 PMC: 9509423. DOI: 10.1111/aji.13600.

A Systematic Review of Extreme Phenotype Strategies to Search for Rare Variants in Genetic Studies of Complex Disorders.

Amanat S, Requena T, Lopez-Escamez J Genes (Basel). 2020; 11(9).

PMID: 32854191 PMC: 7564972. DOI: 10.3390/genes11090987.

Recent advances in the genetics of preterm birth.

Wadon M, Modi N, Wong H, Thapar A, ODonovan M Ann Hum Genet. 2019; 84(3):205-213.

PMID: 31853956 PMC: 7187167. DOI: 10.1111/ahg.12373.

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