title: Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations.
abstract: OBJECTIVE
  We hypothesised that some of the genetic risk for gestational diabetes (GDM) is due to the fetal genome affecting maternal glucose concentrations. Previously, we found associations between fetal IGF2 gene variants and maternal glucose concentrations in late pregnancy.
  
  
  METHODS
  In the present study, we tested associations between SNP alleles from 15 fetal imprinted genes and maternal glucose concentrations in late pregnancy in the Cambridge Baby Growth and Wellbeing cohorts (1160 DNA trios).
  
  
  RESULTS
  Four fetal SNP alleles with the strongest univariate associations: paternally-transmitted IGF2 rs10770125 (P-value=2×10-4) and INS rs2585 (P-value=7×10-4), and maternally-transmitted KCNQ1(OT1) rs231841 (P-value=1×10-3) and KCNQ1(OT1) rs7929804 (P-value=4×10-3), were used to construct a composite fetal imprinted gene allele score which was associated with maternal glucose concentrations (P-value=4.3×10-6, n=981, r2=2.0%) and GDM prevalence (odds ratio per allele 1.44 (1.15, 1.80), P-value=1×10-3, n=89 cases and 899 controls). Meta-analysis of the associations including data from 1367 Hyperglycaemia and Adverse Pregnancy Outcome Study participants confirmed the paternally-transmitted fetal IGF2/INS SNP associations (rs10770125, P-value=3.2×10-8, rs2585, P-value=3.6×10-5) and the composite fetal imprinted gene allele score association (P-value=1.3×10-8), but not the maternally-transmitted fetal KCNQ1(OT1) associations (rs231841, P-value=0.4; rs7929804, P-value=0.2).
  
  
  CONCLUSIONS
  This study suggests that polymorphic variation in fetal imprinted genes, particularly in the IGF2/INS region, contribute a small but significant part to the risk of raised late pregnancy maternal glucose concentrations.
authors.affiliation: Department of Paediatrics, Box 116, Addenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UK. Electronic address: cjp1002@cam.ac.uk.
authors.forename: C J
authors.initials: CJ
authors.lastname: Petry
authors.affiliation: Department of Paediatrics, Box 116, Addenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UK.
authors.forename: K
authors.initials: K
authors.lastname: Mooslehner
authors.affiliation: Department of Paediatrics, Box 116, Addenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UK.
authors.forename: P
authors.initials: P
authors.lastname: Prentice
authors.affiliation: Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Hayes
authors.affiliation: Division of Biostatistics, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nodzenski
authors.affiliation: Division of Biostatistics, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Scholtens
authors.affiliation: Department of Paediatrics, Box 116, Addenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UK.
authors.forename: I A
authors.initials: IA
authors.lastname: Hughes
authors.affiliation: Department of Paediatrics, Box 116, Addenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: Acerini
authors.affiliation: Department of Paediatrics, Box 116, Addenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UK; Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, UK.
authors.forename: K K
authors.initials: KK
authors.lastname: Ong
authors.affiliation: Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: W L
authors.initials: WL
authors.lastname: Lowe
authors.affiliation: Department of Paediatrics, Box 116, Addenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UK; Medical Research Laboratories, The Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: D B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D000328:Adult; D000483:Alleles; D001786:Blood Glucose / Q000235:genetics*; D016640:Diabetes, Gestational / Q000097:blood / Q000235:genetics*; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D007328:Insulin / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011256:Pregnancy Outcome
chemical_list: D001786:Blood Glucose; C035170:IGF2 protein, human; D007328:Insulin; D051657:KCNQ1 Potassium Channel; D007335:Insulin-Like Growth Factor II
keywords: Gestational diabetes; KCNQ1; Meta-analysis; Placenta