TY - JOUR
T1 - A genome-wide association study identifies only two ancestry specific variants associated with spontaneous preterm birth
AU - Rappoport, Nadav
AU - Toung, Jonathan
AU - Hadley, Dexter
AU - Wong, Ronald J.
AU - Fujioka, Kazumichi
AU - Reuter, Jason
AU - Abbott, Charles W.
AU - Oh, Sam
AU - Hu, Donglei
AU - Eng, Celeste
AU - Huntsman, Scott
AU - Bodian, Dale L.
AU - Niederhuber, John E.
AU - Hong, Xiumei
AU - Zhang, Ge
AU - Sikora-Wohfeld, Weronika
AU - Gignoux, Christopher R.
AU - Wang, Hui
AU - Oehlert, John
AU - Jelliffe-Pawlowski, Laura L.
AU - Gould, Jeffrey B.
AU - Darmstadt, Gary L.
AU - Wang, Xiaobin
AU - Bustamante, Carlos D.
AU - Snyder, Michael P.
AU - Ziv, Elad
AU - Patsopoulos, Nikolaos A.
AU - Muglia, Louis J.
AU - Burchard, Esteban
AU - Shaw, Gary M.
AU - O'Brodovich, Hugh M.
AU - Stevenson, David K.
AU - Butte, Atul J.
AU - Sirota, Marina
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-017-18246-5
DO - 10.1038/s41598-017-18246-5
M3 - Article
C2 - 29317701
AN - SCOPUS:85040578611
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 226
ER -