A genome-wide association study identifies only two ancestry specific variants associated with spontaneous preterm birth

Scientific Reports
Nadav RappoportMarina Sirota

Abstract

Preterm birth (PTB), or the delivery prior to 37 weeks of gestation, is a significant cause of infant morbidity and mortality. Although twin studies estimate that maternal genetic contributions account for approximately 30% of the incidence of PTB, and other studies reported fetal gene polymorphism association, to date no consistent associations have been identified. In this study, we performed the largest reported genome-wide association study analysis on 1,349 cases of PTB and 12,595 ancestry-matched controls from the focusing on genomic fetal signals. We tested over 2 million single nucleotide polymorphisms (SNPs) for associations with PTB across five subpopulations: African (AFR), the Americas (AMR), European, South Asian, and East Asian. We identified only two intergenic loci associated with PTB at a genome-wide level of significance: rs17591250 (P = 4.55E-09) on chromosome 1 in the AFR population and rs1979081 (P = 3.72E-08) on chromosome 8 in the AMR group. We have queried several existing replication cohorts and found no support of these associations. We conclude that the fetal genetic contribution to PTB is unlikely due to single common genetic variant, but could be explained by interactions of multiple common variants...Continue Reading

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Citations

Nov 7, 2018·Scientific Data·Marina SirotaUNKNOWN March of Dimes Prematurity Research Centers
Jun 14, 2019·PLoS Genetics·Heli TiensuuMika Rämet
Dec 20, 2019·Annals of Human Genetics·Megan WadonMichael C O'Donovan
Apr 26, 2020·The Journal of Perinatal & Neonatal Nursing·Alexandra L NowakShannon L Gillespie
Oct 26, 2018·Pediatric Research·Mikko HallmanMika Rämet
Jan 21, 2021·Reproductive Sciences·Jagyashila Das, Arindam Maitra
Dec 9, 2020·Human Molecular Genetics·Pol Sole-NavaisBo Jacobsson
Feb 13, 2021·Trends in Molecular Medicine·Camilo EspinosaUNKNOWN Prematurity Research Center at Stanford
Jun 10, 2021·NPJ Genomic Medicine·Esha Bhattacharjee, Arindam Maitra

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Methods Mentioned

BETA
exome sequencing
PCA
genotyping

Software Mentioned

LocusZoom
SNPTEST2
EIGENSTRAT
R
PLINK
EAGLE2
qqman
GenomeStudio
Complete Genomics
IMPUTE2

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