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Genetic Factors and Risk of Preterm Birth

N Engl J Med; 2017 Sep 21; Zhang, et al

In a large sample of women of European ancestry, variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. The genomewide association study included 43,568 women and used gestational duration as a continuous trait and term or preterm (<37 weeks) birth as a dichotomous outcome. Samples from 3 Nordic data sets (n=8,643 women) were used to test for replication of genomic loci that had significant genomewide association or an association with suggestive significance. Researchers found:

  • 4 loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration.
  • Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor.
  • The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication set.
  • Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance.

Citation:

Zhang G, Feenstra B, Bacelis J, et al. Genetic associations with gestational duration and spontaneous preterm birth. N Engl J Med. 2017;377:1156-1167. doi:10.1056/NEJMoa1612665.

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