Pulse Brain · Growing Health Evidence Index
Tier 1 — Meta-analysis / systematic reviewPeer-reviewed

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

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 Bačelis, Maria Carolina Borges, Ge Zhang, Bruce 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, Håkon Håkonarson, M. Geoffrey Hayes, Denise Scholtens, Fernando Rivadeneira, Vincent W. V. Jaddoe, Rebecca Vinding, Hans Bisgaard, Bridget Knight, Katja Pahkala, Olli T. 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 Lyytikäinen, Klaus Bønnelykke, Martine Vrijheid, Janine F. Felix, William L. Lowe, Struan F.A. Grant, Elina Hyppönen, Bo Jacobsson, Marjo‐Riitta Järvelin, Louis J. Muglia, Jeffrey C. Murray, Rachel M. Freathy, Thomas Werge, Mads Melbye, Alfonso Buil, Bjarke Feenstra

Nature Communications · 2019

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Summary

This international meta-analysis of 84,689 infants identified a fetal genetic locus on chromosome 2q13 associated with gestational duration, with replication in an additional 9,291 infants. The association is driven by fetal rather than maternal genotype, and functional studies show the lead variant alters binding of the HIC1 transcriptional repressor at genes encoding interleukin-1 family members, which play roles in pro-inflammatory pathways central to parturition. The findings contribute to understanding of the genetic architecture of pregnancy duration and suggest potential mechanisms linking fetal immunity to the timing of labour.

Regional applicability

The study's findings are relevant to UK maternal and neonatal health policy, as gestational duration outside the term window is associated with increased morbidity and mortality. Understanding fetal genetic contributions to pregnancy duration may inform future risk stratification and counselling in UK obstetric practice, though the clinical utility of individual SNP testing remains to be established.

Key measures

Fetal genome-wide association signals; gestational duration (continuous); early preterm birth, preterm birth, and postterm birth (binary outcomes); SNP rs7594852 effect on HIC1 transcriptional repressor binding

Outcomes reported

The study identified a fetal genome-wide association locus on chromosome 2q13 associated with gestational duration and preterm/postterm birth outcomes. Functional experiments characterised how the lead SNP (rs7594852) alters transcriptional regulation at pro-inflammatory genes involved in parturition.

Theme
Nutrition & health
Subject
Maternal, infant & child nutrition
Study type
Meta-analysis
Study design
Meta-analysis
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1038/s41467-019-11881-8
Catalogue ID
SNmoj1y44j-j6uky2

Topic tags

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