A genome-wide association study identifies only two ancestry specific variants associated with spontaneous preterm birth.
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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, or of rare variants affected by environmental influences, all not detectable using a GWAS alone. |
Year of Publication | 2018
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Journal | Sci Rep
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Volume | 8
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Issue | 1
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Pages | 226
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Date Published | 2018 01 09
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ISSN | 2045-2322
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DOI | 10.1038/s41598-017-18246-5
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PubMed ID | 29317701
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PubMed Central ID | PMC5760643
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Grant list | R21 HD066471 / HD / NICHD NIH HHS / United States
U01 LM012675 / LM / NLM NIH HHS / United States
K12 HL119997 / HL / NHLBI NIH HHS / United States
R25 MD006832 / MD / NIMHD NIH HHS / United States
R01 HL104608 / HL / NHLBI NIH HHS / United States
T32 HG000044 / HG / NHGRI NIH HHS / United States
R21 ES011666 / ES / NIEHS NIH HHS / United States
R21 ES024844 / ES / NIEHS NIH HHS / United States
R01 HD041702 / HD / NICHD NIH HHS / United States
P50 HG007735 / HG / NHGRI NIH HHS / United States
R01 HL117004 / HL / NHLBI NIH HHS / United States
P60 MD006902 / MD / NIMHD NIH HHS / United States
K01 LM012381 / LM / NLM NIH HHS / United States
RC2 HL101748 / HL / NHLBI NIH HHS / United States
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