Oral Annual Conference of the Genetics Society of Australasia with the NZ Society for Biochemistry & Molecular Biology

GWAS on Post-term Birth: Analysis of Successive Finnish Birth Cohorts Identifies TKT and SSBP2 Loci (720)

William Schierding 1 , Jisha Antony 2 , Ville Karhunen 3 4 , Marja Vääräsmäki 3 4 , Steve Franks 3 4 , Paul Elliott 3 4 , Eero Kajantie 3 4 , Sylvain Sebert 3 4 , Alex Blakemore 3 4 , Julia A Horsfield 2 , Marjo-Riitta Järvelin 3 4 , Justin M O’Sullivan 1 , Wayne S Cutfield 1
  1. University of Auckland, Auckland, New Zealand
  2. Department of Pathology, Dunedin School of Medicine, The University of Otago, Dunedin, New Zealand
  3. Department of Epidemiology and Biostatistics, MRC–PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, UK
  4. Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland

Gestation is a critical time-point in human development. Deviations from the 37-41 weeks that form the healthy gestational age at birth correlate with both acute and long-term health effects for the child. Both short and long gestational ages at birth (i.e. pre- and post-term, respectively) affect a significant portion of the population (rates vary between populations, but each affect over 5% of the population). Additionally, both are heritable and are influenced by the pre- and perinatal environment (i.e. infection status, nutrition, antepartum bleeding, twins). Despite the heritable component, the specific genetic influences underlying differences in gestational age are poorly understood. This study identifies genetic variants within the introns of TKT, ARGHAP42, and ADAMTS13 genes and intergenic upstream (5’) of the B3GALT5 and SSBP2 genes that are associated with prolonged gestation in 9,141 Northern Finnish (white European) individuals from two birth cohorts (i.e. 1966 and 1986). Spatial and mRNA expression analyses identify the regulatory affects and corresponding consequences of post-term birth. The variants in the B3GALT5, ADAMTS13, and TKT loci are linked to alterations in gene expression levels (i.e. cis-eQTLs) with the nearest genes. The SSBP2 and ARGHAP42 loci were not found to be associated with expression differences of the nearest genes. These five loci also have putative effects on the regulation of processes involved in human development such as growth and metabolism, and, more specifically, hematopoiesis. Overall, our findings provide the first evidence of a specific genetic influence associated with prolonged gestation, including putative explanations of the underlying biological cause.