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

Xueping Liu¹, Dorte Helenius^{2

3}, Line Skotte¹, Robin N Beaumont⁴, Matthias Wielscher⁵, Frank Geller¹, Julius Juodakis⁶, Anubha Mahajan⁷, Jonathan P Bradfield^{8

9}, Frederick T J Lin¹⁰, Suzanne Vogelezang^{11

12

13}, Mariona Bustamante^{14

15

16}, Tarunveer S Ahluwalia¹⁷, Niina Pitkänen¹⁸, Carol A Wang¹⁹, Jonas Bacelis²⁰, Maria C Borges^{21

22}, Ge Zhang^{23

24

25}, Bruce A Bedell²⁶, Robert M Rossi^{25

27}, Kristin Skogstrand^{2

28}, Shouneng Peng^{29

30}, Wesley K Thompson^{2

3}, Vivek Appadurai^{2

3}, Debbie A Lawlor^{21

22

31}, Ilkka Kalliala^{32

33}, Christine Power³⁴, Mark I McCarthy^{7

35

36}, Heather A Boyd¹, Mary L Marazita^{37

38}, Hakon Hakonarson^{8

39

40}, M Geoffrey Hayes^{10

41

42}, Denise M Scholtens⁴³, Fernando Rivadeneira^{11

13

44}, Vincent W V Jaddoe^{11

12

13}, Rebecca K Vinding¹⁷, Hans Bisgaard¹⁷, Bridget A Knight⁴⁵, Katja Pahkala^{18

46}, Olli Raitakari^{18

47}, Øyvind Helgeland^{48

49

50}, Stefan Johansson^{48

51}, Pål R Njølstad^{48

49}, João Fadista^{1

52}, Andrew J Schork^{2

3}, Ron Nudel^{2

3}, Daniel E Miller⁵³, Xiaoting Chen⁵³, Matthew T Weirauch^{27

53

54}, Preben Bo Mortensen^{2

55

56}, Anders D Børglum^{2

56

57}, Merete Nordentoft^{2

58

59}, Ole Mors^{2

60}, Ke Hao^{29

30}, Kelli K Ryckman^{26

61}, David M Hougaard^{2

28}, Leah C Kottyan^{27

53}, Craig E Pennell¹⁹, Leo-Pekka Lyytikainen^{62

63}, Klaus Bønnelykke¹⁷, Martine Vrijheid^{14

15

16}, Janine F Felix^{11

12

13}, William L Lowe Jr¹⁰, Struan F A Grant^{8

39

40}, Elina Hyppönen^{34

64

65}, Bo Jacobsson^{6

66}, Marjo-Riitta Jarvelin^{67

68}, Louis J Muglia^{23

24

26

27}, Jeffrey C Murray²⁶, Rachel M Freathy^{4

69}, Thomas M Werge^{2

3

59}, Mads Melbye^{1

59

70}, Alfonso Buil^{2

3}, Bjarke Feenstra⁷¹

Affiliations

¹ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
² iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
³ Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
⁴ Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
⁵ Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
⁶ Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁷ Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
⁸ Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁹ Quantinuum Research, LLC, San Diego, CA, USA.
¹⁰ Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹¹ The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹² Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹³ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹⁴ ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain.
¹⁵ Universitat Pompeu Fabra (UPF), Barcelona, Spain.
¹⁶ CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
¹⁷ COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
¹⁸ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20520, Turku, Finland.
¹⁹ School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle, Newcastle, NSW, Australia.
²⁰ Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Gothenburg, Sweden.
²¹ MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
²² Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
²³ Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
²⁴ Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
²⁵ March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, OH, USA.
²⁶ Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
²⁷ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
²⁸ Statens Serum Institut, Center for Neonatal Screening, Department for Congenital Disorders, Copenhagen, Denmark.
²⁹ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY, 10029, USA.
³⁰ Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY, 10029, USA.
³¹ NIHR Bristol Biomedical Research Centre, Bristol, UK.
³² Department of Surgery and Cancer, IRDB, Faculty of Medicine, Imperial College, London, W12 0NN, UK.
³³ Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu, 200029 HUS, Finland.
³⁴ Population, Policy and Practice, Great Ormond Street Institute for Child Health, University College London, London, UK.
³⁵ Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, OX3 7LJ, UK.
³⁶ NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, OX3 7LJ, UK.
³⁷ Center for Craniofacial and Dental Genetics, Department of Oral Biology School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
³⁸ Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
³⁹ Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁴⁰ Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁴¹ Department of Anthropology, Northwestern University, Evanston, IL, USA.
⁴² Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁴³ Division of Biostatistics, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁴⁴ Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁴⁵ NIHR Exeter Clinical Research Facility, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
⁴⁶ Paavo Nurmi Centre, Sports & Exercise Medicine Unit, Department of Health and Physical Activity, University of Turku, 20520, Turku, Finland.
⁴⁷ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, 20521, Turku, Finland.
⁴⁸ K. G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
⁴⁹ Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
⁵⁰ Norwegian Institute of Public Health, Division of Health data and Digitalization, Department of Genetic Research and Bioinformatics, Oslo, Norway.
⁵¹ Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
⁵² Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden.
⁵³ Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁵⁴ Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital, Cincinnati, OH, USA.
⁵⁵ National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark.
⁵⁶ iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.
⁵⁷ Department of Biomedicine-Human Genetics, Aarhus University, Aarhus, Denmark.
⁵⁸ Mental Health Center Copenhagen, Mental Health Services in the Capital Region of Denmark, Copenhagen, Denmark.
⁵⁹ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁶⁰ Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
⁶¹ Department of Epidemiology, University of Iowa, Iowa City, IA, USA.
⁶² Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33520, Finland.
⁶³ Department of Clinical Chemistry, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, 33014, Tampere, Finland.
⁶⁴ Australian Centre for Precision Health, University of South Australia Cancer Research Institute, Adelaide, Australia.
⁶⁵ South Australian Health and Medical Research Institute, Adelaide, Australia.
⁶⁶ Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
⁶⁷ Institute of Health Sciences, University of Oulu, Oulu, Finland.
⁶⁸ Department of Epidemiology and Biostatistics, School of Public Health, Medical Research Council-Health Protection Agency Centre for Environment and Health, Faculty of Medicine, Imperial College London, London, UK.
⁶⁹ Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
⁷⁰ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁷¹ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. fee@ssi.dk.

PMID: 31477735
PMCID: PMC6718389
DOI: 10.1038/s41467-019-11881-8

Meta-Analysis

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

Xueping Liu et al. Nat Commun. 2019.

. 2019 Sep 2;10(1):3927.

doi: 10.1038/s41467-019-11881-8.

Authors

Affiliations

¹ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
² iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
³ Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
⁴ Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
⁵ Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
⁶ Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁷ Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
⁸ Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁹ Quantinuum Research, LLC, San Diego, CA, USA.
¹⁰ Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹¹ The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹² Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹³ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹⁴ ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain.
¹⁵ Universitat Pompeu Fabra (UPF), Barcelona, Spain.
¹⁶ CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
¹⁷ COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
¹⁸ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20520, Turku, Finland.
¹⁹ School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle, Newcastle, NSW, Australia.
²⁰ Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Gothenburg, Sweden.
²¹ MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
²² Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
²³ Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
²⁴ Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
²⁵ March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, OH, USA.
²⁶ Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
²⁷ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
²⁸ Statens Serum Institut, Center for Neonatal Screening, Department for Congenital Disorders, Copenhagen, Denmark.
²⁹ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY, 10029, USA.
³⁰ Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY, 10029, USA.
³¹ NIHR Bristol Biomedical Research Centre, Bristol, UK.
³² Department of Surgery and Cancer, IRDB, Faculty of Medicine, Imperial College, London, W12 0NN, UK.
³³ Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu, 200029 HUS, Finland.
³⁴ Population, Policy and Practice, Great Ormond Street Institute for Child Health, University College London, London, UK.
³⁵ Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, OX3 7LJ, UK.
³⁶ NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, OX3 7LJ, UK.
³⁷ Center for Craniofacial and Dental Genetics, Department of Oral Biology School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
³⁸ Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
³⁹ Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁴⁰ Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁴¹ Department of Anthropology, Northwestern University, Evanston, IL, USA.
⁴² Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁴³ Division of Biostatistics, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁴⁴ Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁴⁵ NIHR Exeter Clinical Research Facility, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
⁴⁶ Paavo Nurmi Centre, Sports & Exercise Medicine Unit, Department of Health and Physical Activity, University of Turku, 20520, Turku, Finland.
⁴⁷ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, 20521, Turku, Finland.
⁴⁸ K. G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
⁴⁹ Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
⁵⁰ Norwegian Institute of Public Health, Division of Health data and Digitalization, Department of Genetic Research and Bioinformatics, Oslo, Norway.
⁵¹ Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
⁵² Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden.
⁵³ Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁵⁴ Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital, Cincinnati, OH, USA.
⁵⁵ National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark.
⁵⁶ iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.
⁵⁷ Department of Biomedicine-Human Genetics, Aarhus University, Aarhus, Denmark.
⁵⁸ Mental Health Center Copenhagen, Mental Health Services in the Capital Region of Denmark, Copenhagen, Denmark.
⁵⁹ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁶⁰ Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
⁶¹ Department of Epidemiology, University of Iowa, Iowa City, IA, USA.
⁶² Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33520, Finland.
⁶³ Department of Clinical Chemistry, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, 33014, Tampere, Finland.
⁶⁴ Australian Centre for Precision Health, University of South Australia Cancer Research Institute, Adelaide, Australia.
⁶⁵ South Australian Health and Medical Research Institute, Adelaide, Australia.
⁶⁶ Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
⁶⁷ Institute of Health Sciences, University of Oulu, Oulu, Finland.
⁶⁸ Department of Epidemiology and Biostatistics, School of Public Health, Medical Research Council-Health Protection Agency Centre for Environment and Health, Faculty of Medicine, Imperial College London, London, UK.
⁶⁹ Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
⁷⁰ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁷¹ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. fee@ssi.dk.

PMID: 31477735
PMCID: PMC6718389
DOI: 10.1038/s41467-019-11881-8

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.

PubMed Disclaimer

Conflict of interest statement

D.A.L. received support from Roche Diagnostics and Medtronic for biomarker research unrelated to the work presented in this paper. M.I.M. serves on advisory panels for Pfizer, NovoNordisk, Zoe Global; has received honoraria from Merck, Pfizer, NovoNordisk, and Eli Lilly; has stock options in Zoe Global; has received research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier & Takeda. S.F.A.G. has received support from GSK for research that is not related to the study presented in this paper. T.M.W. has acted as lecturer and scientific advisor to H. Lundbeck A/S. The remaining authors declare no competing interests.

Figures

**Fig. 1**
Discovery stage results at the 2q13 locus. Regional association plots for a gestational duration and b postterm birth. SNP position is shown on the x-axis and association (−log10 P value) with gestational duration and postterm birth, respectively, on the left y-axis. The lead SNP, rs7594852, from the gestational duration analysis is represented by a purple diamond, and the other SNPs are colored to reflect their LD with the lead SNP (based on pairwise r² values from the Danish National Birth Cohort). In the postterm birth analysis, rs7607470 had a slightly lower P value, but this SNP is highly correlated with rs7594852 (r² > 0.99), and the latter SNP was selected for the replication stage analyses of both gestational duration and postterm birth. Estimated recombination rates are from HapMap (right y-axis)

**Fig. 2**
Forest plots showing association results for rs7594852. a Gestational duration effect estimates with 95% CIs, and b postterm birth ORs with 95% CIs. Source data are provided as a Source Data file

**Fig. 3**
HIC1 binding at the 2q13 locus. a The rs7594852-C allele creates a stronger binding site for the hypermethylated in cancer 1 (HIC1) protein. The sequence logo of the HIC1-binding motif shows the DNA binding preferences of HIC1. Tall nucleotides above the dashed line indicate DNA bases that are preferred by HIC1, whereas bases below the dashed line are disfavored. The y-axis indicates the relative free energies of binding for each nucleotide at each position. The height of each nucleotide can be interpreted as the free energy difference from the average (ΔΔG) in units of gas constant (R) and temperature (T). The DNA sequence flanking the rs7594852-C allele is shown directly below, with the alternative rs7594852-T allele shown at the bottom. The rs7594852-T allele changes the HIC1 binding site sequence from C (most favored) to T (less favored). b UC Santa Cruz Genome Browser screenshot depicting the rs7594852 locus. The purple (*CKAP2L*) and black (*IL1A*) graphics at the top indicate the locations of exons (columns), untranslated regions (rectangles), and introns (horizontal lines), with arrows indicating the direction of transcription. The red vertical line indicates the position of rs7594852, which overlaps strong signals obtained from chromatin immunoprecipitation sequencing (ChIP-seq) experiments (indicating histone modification by mono-, di-, or trimethylation of histone H3 on lysine 4; H3K4) in trophoblast cultured cells, placental amnion, or fetal placenta. c Experimental validation of allele-dependent binding of human purified recombinant HIC1 protein with a c-Myc/DDK tag to rs7594852 and flanking sequence via electrophoretic mobility shift assay (EMSA). Arrows indicate allele-dependent binding of HIC1 (bottom arrow) and a supershift of the protein–DNA complex induced by the binding of the anti-DDK antibody to the complex (top arrow). The presence of multiple bands in lanes 3 and 4 is likely due to the presence of multiple HIC1 isoforms. Source data are provided as a Source Data file

See this image and copyright information in PMC

References

1. Moffett A, Loke C. Immunology of placentation in eutherian mammals. Nat. Rev. Immunol. 2006;6:584–594. doi: 10.1038/nri1897. - DOI - PubMed
1. Smith R. Parturition. N. Engl. J. Med. 2007;356:271–283. doi: 10.1056/NEJMra061360. - DOI - PubMed
1. Medawar PB. Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates. Symp. Soc. Exp. Biol. 1953;7:320–338.
1. Gundling WE, Wildman DE. A review of inter- and intraspecific variation in the eutherian placenta. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2015;370:20140072. doi: 10.1098/rstb.2014.0072. - DOI - PMC - PubMed
1. Racicot K, Kwon JY, Aldo P, Silasi M, Mor G. Understanding the complexity of the immune system during pregnancy. Am. J. Reprod. Immunol. 2014;72:107–116. doi: 10.1111/aji.12289. - DOI - PMC - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources