University of Oulu

Schierding W, Antony J, Karhunen V, et al GWAS on prolonged gestation (post-term birth): analysis of successive Finnish birth cohorts, Journal of Medical Genetics 2018; 55:55-63

GWAS on prolonged gestation (post-term birth) : analysis of successive Finnish birth cohorts

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Author: Schierding, William1,2; Antony, Jisha3; Karhunen, Ville4,5,6,7;
Organizations: 1Liggins Institute, University of Auckland, Auckland, New Zealand
2Gravida: National Centre for Growth and Development, University of Auckland, Auckland, New Zealand
3Department of Pathology, Dunedin School of Medicine, The University of Otago, Dunedin, 9016, New Zealand
4Center for Life Course Health Research, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland
5Biocenter Oulu, University of Oulu, Finland
6Department of Epidemiology and Biostatistics, MRC–PHE Centre for Environment & Health, School of Public Health, Imperial College London, Norfolk Place, W21PG London, UK
7Unit of Primary Care, Oulu University Hospital, Oulu, Finland
8PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, 90014 Oulu, Finland
9National Institute for Health and Welfare, Chronic Disease Prevention Unit, 00271 Helsinki and 90101 Oulu, Finland
10Children’s Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
11Department of Genomics of Complex Diseases School of Public Health, Imperial College London, UK
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2019092029098
Language: English
Published: BMJ, 2018
Publish Date: 2019-09-20
Description:

Abstract

Background: Gestation is a crucial timepoint in human development. Deviation from a term gestational age correlates with both acute and longterm adverse health effects for the child. Both being born pre-term and post-term, that is, having short and long gestational ages, are heritable and influenced by the prenatal and perinatal environment. Despite the obvious heritable component, specific genetic influences underlying differences in gestational age are poorly understood.

em>Methods: We investigated the genetic architecture of gestational age in 9141 individuals, including 1167 born post-term, across two Northern Finland cohorts born in 1966 or 1986.

Results: Here we identify one globally significant intronic genetic variant within the ADAMTS13 gene that is associated with prolonged gestation (p=4.85×10−8). Additional variants that reached suggestive levels of significance were identified within introns at the ARGHAP42 and TKT genes, and in the upstream (5’) intergenic regions of the B3GALT5 and SSBP2 genes. The variants near the ADAMTS13, B3GALT5, SSBP2 and TKT loci are linked to alterations in gene expression levels (cis-eQTLs). Luciferase assays confirmed the allele specific enhancer activity for the BGALT5 and TKT loci.

Conclusions: Our findings provide the first evidence of a specific genetic influence associated with prolonged gestation. This study forms a foundation for a better understanding of the genetic and long-term health risks faced by induced and post-term individuals. The long-term risks for induced individuals who have a previously overlooked post-term potential may be a major issue for current health providers.

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Series: Journal of medical genetics
ISSN: 0022-2593
ISSN-E: 1468-6244
ISSN-L: 0022-2593
Volume: 55
Issue: 1
Pages: 55 - 63
DOI: 10.1136/jmedgenet-2017-104880
OADOI: https://oadoi.org/10.1136/jmedgenet-2017-104880
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
Copyright information: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.