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

被引:35
作者
Rappoport, Nadav [1 ,2 ]
Toung, Jonathan [3 ]
Hadley, Dexter [1 ,2 ]
Wong, Ronald J. [3 ]
Fujioka, Kazumichi [3 ]
Reuter, Jason [4 ]
Abbott, Charles W. [4 ]
Oh, Sam [5 ]
Hu, Donglei
Eng, Celeste [5 ]
Huntsman, Scott [5 ]
Bodian, Dale L. [6 ]
Niederhuber, John E. [6 ,7 ]
Hong, Xiumei [7 ]
Zhang, Ge [8 ]
Sikora-Wohfeld, Weronika [3 ]
Gignoux, Christopher R. [4 ]
Wang, Hui [3 ]
Oehlert, John [3 ]
Jelliffe-Pawlowski, Laura L. [9 ]
Gould, Jeffrey B. [3 ]
Darmstadt, Gary L. [3 ]
Wang, Xiaobin [7 ]
Bustamante, Carlos D. [4 ]
Snyder, Michael P. [4 ]
Ziv, Elad [5 ]
Patsopoulos, Nikolaos A. [10 ,11 ,12 ]
Muglia, Louis J. [8 ]
Burchard, Esteban [5 ]
Shaw, Gary M. [3 ]
O'Brodovich, Hugh M. [3 ]
Stevenson, David K. [3 ]
Butte, Atul J. [1 ,2 ,5 ]
Sirota, Marina [1 ,2 ,5 ]
机构
[1] Univ Calif San Francisco, Inst Computat Hlth Sci, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA
[3] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA
[4] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA
[5] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA
[6] Inova Translat Med Inst, Inova Hlth Syst, Falls Church, VA USA
[7] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Early Life Origins Dis, Dept Populat Family & Reprod Hlth, Baltimore, MD USA
[8] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA
[9] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA
[10] Brigham & Womens Hosp, Dept Neurol, Syst Biol & Comp Sci Program, Div Genet,Ann Romney Ctr Neurol Dis, Boston, MA USA
[11] Harvard Med Sch, Boston, MA USA
[12] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA
关键词
YOUNG MATERNAL AGE; BODY-MASS INDEX; TUMOR-NECROSIS-FACTOR; RISK-FACTORS; GENETIC CONTRIBUTIONS; RACIAL DISPARITIES; SURFACTANT THERAPY; AIR-POLLUTION; WEIGHT; DELIVERY;
D O I
10.1038/s41598-017-18246-5
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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页数:11
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