Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 are associated with gestational duration
Author:
Liu Xueping, Helenius Dorte, Skotte Line, Beaumont Robin N., Wielscher Matthias, Geller Frank, Juodakis Julius, Mahajan Anubha, Bradfield Jonathan P., Lin Frederick T.J., Vogelezang Suzanne, Bustamante Mariona, Ahluwalia Tarunveer S.ORCID, Pitkänen NiinaORCID, Wang Carol A., Bacelis Jonas, Borges Maria C., Zhang Ge, Bedell Bruce A., Rossi Robert M., Skogstrand Kristin, Peng Shouneng, Thompson Wesley K., Appadurai Vivek, Lawlor Debbie A., Kalliala Ilkka, Power Christine, McCarthy Mark I., Boyd Heather A., Marazita Mary L., Hakonarson Hakon, Hayes M. Geoffrey, Scholtens Denise M., Rivadeneira Fernando, Jaddoe Vincent W.V., Vinding Rebecca K., Bisgaard Hans, Knight Bridget A., Pahkala Katja, Raitakari Olli, Helgeland Øyvind, Johansson Stefan, Njølstad Pål R., Fadista João, Schork Andrew, Nudel Ron, Miller Daniel E., Chen XiaotingORCID, Weirauch Matthew T., Mortensen Preben Bo, Børglum Anders D., Nordentoft Merete, Mors Ole, Hao Ke, Ryckman Kelli K., Hougaard David M., Kottyan Leah C., Pennell Craig E., Lyytikainen Leo-Pekka, Bønnelykke Klaus, Vrijheid Martine, Felix Janine F., Lowe William L., Grant Struan F.A., Hyppönen Elina, Jacobsson Bo, Jarvelin Marjo-Riitta, Muglia Louis J., Murray Jeffrey C., Freathy Rachel M., Werge Thomas M., Melbye Mads, Buil Alfonso, Feenstra BjarkeORCID, ,
Abstract
AbstractThe duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. We conducted 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 was associated with gestational duration; the association was replicated in 9,291 additional infants (combined P = 3.96 × 10−14). Analysis of 15,536 mother-child pairs showed that the association was driven by fetal rather than maternal genotype. Functional experiments showed 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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