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Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.

Journal article
Authors Xueping Liu
Dorte Helenius
Line Skotte
Robin N Beaumont
Matthias Wielscher
Frank Geller
Julius Juodakis
Anubha Mahajan
Jonathan P Bradfield
Frederick T J Lin
Suzanne Vogelezang
Mariona Bustamante
Tarunveer S Ahluwalia
Niina Pitkänen
Carol A Wang
Jonas Bacelis
Maria C Borges
Ge Zhang
Bruce A Bedell
Robert M Rossi
Kristin Skogstrand
Shouneng Peng
Wesley K Thompson
Vivek Appadurai
Debbie A Lawlor
Ilkka Kalliala
Christine Power
Mark I McCarthy
Heather A Boyd
Mary L Marazita
Hakon Hakonarson
M Geoffrey Hayes
Denise M Scholtens
Fernando Rivadeneira
Vincent W V Jaddoe
Rebecca K Vinding
Hans Bisgaard
Bridget A Knight
Katja Pahkala
Olli Raitakari
Øyvind Helgeland
Stefan Johansson
Pål R Njølstad
João Fadista
Andrew J Schork
Ron Nudel
Daniel E Miller
Xiaoting Chen
Matthew T Weirauch
Preben Bo Mortensen
Anders D Børglum
Merete Nordentoft
Ole Mors
Ke Hao
Kelli K Ryckman
David M Hougaard
Leah C Kottyan
Craig E Pennell
Leo-Pekka Lyytikainen
Klaus Bønnelykke
Martine Vrijheid
Janine F Felix
William L Lowe
Struan F A Grant
Elina Hyppönen
Bo Jacobsson
Marjo-Riitta Jarvelin
Louis J Muglia
Jeffrey C Murray
Rachel M Freathy
Thomas M Werge
Mads Melbye
Alfonso Buil
Bjarke Feenstra
Published in Nature communications
Volume 10
Issue 1
Pages 3927
ISSN 2041-1723
Publication year 2019
Published at Institute of Clinical Sciences, Department of Obstetrics and Gynecology
Pages 3927
Language en
Links dx.doi.org/10.1038/s41467-019-11881...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Obstetrics and gynaecology

Abstract

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.

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