Variants at the ADAMTS13, BGALT5, SSBP2 and TKT Loci are associated with Post-term birth

Abstract

AbstractGestation is a crucial timepoint in human development. Deviation from a term gestational age correlates with both acute and long-term adverse health effects for the child. Both being born pre and post-term,i.e.having short and long gestational ages, are heritable and influenced by the pre- and perinatal environment. Despite the obvious heritable component, specific genetic influences underlying differences in gestational age are poorly understood. Here we identify one globally significant intronic genetic variant within theADAMTS13gene that is associated with prolonged gestation in 9,141 white European individuals from the 1966 and 1986 Northern Finland birth cohorts. Additional variants that reached suggestive levels of significance were identified within introns at theTKT,andARGHAP42genes, and in the upstream (5’) intergenic regions of theB3GALT5andSSBP2genes. The variants near theADAMTS13, B3GALT5, SSBP2andTKTloci are linked to alterations in gene expression levels (cis-eQTLs). Luciferase assays confirmed the allele specific enhancer activity for theBGALT5andTKTloci. Our findings provide the first evidence of a specific genetic influence associated with prolonged gestation.