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Sci Rep. 2018 Jan 9;8(1):226. doi: 10.1038/s41598-017-18246-5.

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

Author information

1
Institute for Computational Health Sciences, University of California, San Francisco, 94143, CA, USA.
2
Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
3
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
4
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
5
Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
6
Inova Translational Medicine Institute, Inova Health System, Falls Church, VA, USA.
7
Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
8
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
9
Department of Biostatistics, University of California, San Francisco, CA, USA.
10
Systems Biology and Computer Science Program, Ann Romney Center of Neurological Diseases, Department of Neurology, Division of Genetics, Brigham & Women's Hospital, Boston, MA, USA.
11
Harvard Medical School, Boston, MA, USA.
12
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
13
Institute for Computational Health Sciences, University of California, San Francisco, 94143, CA, USA. atul.butte@ucsf.edu.
14
Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA. atul.butte@ucsf.edu.
15
Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA. atul.butte@ucsf.edu.
16
Institute for Computational Health Sciences, University of California, San Francisco, 94143, CA, USA. marina.sirota@ucsf.edu.
17
Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA. marina.sirota@ucsf.edu.
18
Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA. marina.sirota@ucsf.edu.

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.

PMID:
29317701
PMCID:
PMC5760643
DOI:
10.1038/s41598-017-18246-5
[Indexed for MEDLINE]
Free PMC Article

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