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

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Liu , X , Helenius , D , Skotte , L , Beaumont , R N , Wielscher , M , Geller , F , Juodakis , J , Mahajan , A , Bradfield , J P , Lin , F T , Vogelezang , S , Bustamante , M , Ahluwalia , T S , Pitkanen , N , Wang , C A , Bacelis , J , Borges , M C , Zhang , G , Bedell , B A , Rossi , R M , Skogstrand , K , Peng , S , Thompson , W K , Appadurai , V , Lawlor , D A , Kalliala , I , Power , C , McCarthy , M , Boyd , H A , Marazita , M L , Hakonarson , H , Hayes , M G , Scholtens , D M , Rivadeneira , F , Jaddoe , V W V , Vinding , R K , Bisgaard , H , Knight , B A , Pahkala , K , Raitakari , O , Helgeland , O , Johansson , S , Njolstad , P R , Fadista , J , Schork , A J , Nudel , R , Miller , D E , Chen , X , Weirauch , M T , Mortensen , P B , Borglum , A D , Nordentoft , M , Mors , O , Hao , K , Ryckman , K K , Hougaard , D M , Kottyan , L C , Pennell , C E , Lyytikainen , L-P , Bonnelykke , K , Vrijheid , M , Felix , J F , Lowe , W L , Grant , S F , Hypponen , E , Jacobsson , B , Jarvelin , M-R , Muglia , L J , Murray , J C , Freathy , R M , Werge , T M , Melbye , M , Buil , A & Feenstra , B 2019 , ' Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration ' , Nature Communications , vol. 10 , 3927 . https://doi.org/10.1038/s41467-019-11881-8

Title: Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate 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 Tj; Vogelezang, Suzanne; Bustamante, Mariona; Ahluwalia, Tarunveer S.; Pitkanen, Niina; 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; 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, Oyvind; Johansson, Stefan; Njolstad, Pal R.; Fadista, Joao; Schork, Andrew J.; Nudel, Ron; Miller, Daniel E.; Chen, Xiaoting; Weirauch, Matthew T.; Mortensen, Preben Bo; Borglum, Anders D.; Nordentoft, Merete; Mors, Ole; Hao, Ke; Ryckman, Kelli K.; Hougaard, David M.; Kottyan, Leah C.; Pennell, Craig E.; Lyytikainen, Leo-Pekka; Bonnelykke, Klaus; Vrijheid, Martine; Felix, Janine F.; Lowe, William L.; Grant, Struan Fa; Hypponen, Elina; Jacobsson, Bo; Jarvelin, Marjo-Riitta; Muglia, Louis J.; Murray, Jeffrey C.; Freathy, Rachel M.; Werge, Thomas M.; Melbye, Mads; Buil, Alfonso; Feenstra, Bjarke
Contributor: University of Helsinki, Department of Obstetrics and Gynecology
Date: 2019-09-02
Language: eng
Number of pages: 13
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/305435
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 x 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.
Subject: LD SCORE REGRESSION
PRETERM BIRTH
WIDE ASSOCIATION
FUNCTIONAL VARIATION
SEQUENCE
WEIGHT
GWAS
AGE
EXPRESSION
HAPLOTYPES
3123 Gynaecology and paediatrics
3111 Biomedicine
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