title: Associations Between Fetal Imprinted Genes and Maternal Blood Pressure in Pregnancy.
abstract: In addition to maternal genes and environmental exposures, variation in fetal imprinted genes could also affect maternal blood pressure during pregnancy. Our objective was to test the associations between polymorphic variants in 16 imprinted genes and maternal mean arterial blood pressures in 1160 DNA trios from 2 established birth cohorts (the Cambridge Baby Growth and Wellbeing Studies) and seek replication in 1367 Hyperglycemia and Adverse Pregnancy Outcome Study participants. Significant univariate associations, all independent of fetal sex, were observed in the Cambridge cohorts, including FAM99A rs1489945 transmitted from the mother (P=2×10-4), DLK1 rs10139403 (mother; P=9×10-4), DLK1 rs12147008 (mother; P=1×10-3), H19 rs217222 (father; P=1×10-3), SNRPN rs1453556 (father; P=1×10-3), IGF2 rs6356 (father; P=1×10-3), and NNAT rs6066671 (father; P=1×10-3). In meta-analysis including additional independent Hyperglycemia and Adverse Pregnancy Outcome Study data, the association with maternally transmitted fetal DLK1 rs10139403 reached genome-wide significance (P=6.3×10-10). With the exception of fetal rs1489945 and rs217222, all of other associations were unidirectional and most were statistically significant. To further explore the significance of these relationships, we developed an allele score based on the univariate findings. The score was strongly associated with maternal blood pressure at 31 weeks (P=4.1×10-8; adjusted r2=5.6%) and 37 weeks of pregnancy (P=1.1×10-4; r2=3.6%), and during the last 2 weeks before parturition (P=1.1×10-10; r2=8.7%). It was also associated with gestational hypertension (odds ratio, 1.54 [range, 1.14-2.09] per allele; P=0.005; 45 cases and 549 controls). These data support the concept that fetal imprinted genes are related to the development of gestational hypertension.
authors: From the Department of Paediatrics (C.J.P., N.S.M., G.P., I.A.H., C.L.A., K.K.O., D.B.D.), Medical Research Council Epidemiology Unit (K.K.O.), and Institute of Metabolic Science (D.B.D.), University of Cambridge, United Kingdom; Hospital Sant Joan de Déu, Servicio de Pediatría, Barcelona, Spain (N.S.M.); Divisão de Endocrinologia Pediátrica, Departamento de Pediatria, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (G.P.); and Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine (M.G.H., W.L.L.) and Division of Biostatistics, Department of Preventive Medicine (M.N., D.M.S.), Northwestern University Feinberg School of Medicine, Chicago, IL. cjp1002@cam.ac.uk.
authors: Clive J
authors: CJ
authors: Petry
authors: From the Department of Paediatrics (C.J.P., N.S.M., G.P., I.A.H., C.L.A., K.K.O., D.B.D.), Medical Research Council Epidemiology Unit (K.K.O.), and Institute of Metabolic Science (D.B.D.), University of Cambridge, United Kingdom; Hospital Sant Joan de Déu, Servicio de Pediatría, Barcelona, Spain (N.S.M.); Divisão de Endocrinologia Pediátrica, Departamento de Pediatria, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (G.P.); and Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine (M.G.H., W.L.L.) and Division of Biostatistics, Department of Preventive Medicine (M.N., D.M.S.), Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Nuria
authors: N
authors: Sanz Marcos
authors: From the Department of Paediatrics (C.J.P., N.S.M., G.P., I.A.H., C.L.A., K.K.O., D.B.D.), Medical Research Council Epidemiology Unit (K.K.O.), and Institute of Metabolic Science (D.B.D.), University of Cambridge, United Kingdom; Hospital Sant Joan de Déu, Servicio de Pediatría, Barcelona, Spain (N.S.M.); Divisão de Endocrinologia Pediátrica, Departamento de Pediatria, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (G.P.); and Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine (M.G.H., W.L.L.) and Division of Biostatistics, Department of Preventive Medicine (M.N., D.M.S.), Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Gracielle
authors: G
authors: Pimentel
authors: From the Department of Paediatrics (C.J.P., N.S.M., G.P., I.A.H., C.L.A., K.K.O., D.B.D.), Medical Research Council Epidemiology Unit (K.K.O.), and Institute of Metabolic Science (D.B.D.), University of Cambridge, United Kingdom; Hospital Sant Joan de Déu, Servicio de Pediatría, Barcelona, Spain (N.S.M.); Divisão de Endocrinologia Pediátrica, Departamento de Pediatria, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (G.P.); and Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine (M.G.H., W.L.L.) and Division of Biostatistics, Department of Preventive Medicine (M.N., D.M.S.), Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: M Geoffrey
authors: MG
authors: Hayes
authors: From the Department of Paediatrics (C.J.P., N.S.M., G.P., I.A.H., C.L.A., K.K.O., D.B.D.), Medical Research Council Epidemiology Unit (K.K.O.), and Institute of Metabolic Science (D.B.D.), University of Cambridge, United Kingdom; Hospital Sant Joan de Déu, Servicio de Pediatría, Barcelona, Spain (N.S.M.); Divisão de Endocrinologia Pediátrica, Departamento de Pediatria, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (G.P.); and Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine (M.G.H., W.L.L.) and Division of Biostatistics, Department of Preventive Medicine (M.N., D.M.S.), Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Michael
authors: M
authors: Nodzenski
authors: From the Department of Paediatrics (C.J.P., N.S.M., G.P., I.A.H., C.L.A., K.K.O., D.B.D.), Medical Research Council Epidemiology Unit (K.K.O.), and Institute of Metabolic Science (D.B.D.), University of Cambridge, United Kingdom; Hospital Sant Joan de Déu, Servicio de Pediatría, Barcelona, Spain (N.S.M.); Divisão de Endocrinologia Pediátrica, Departamento de Pediatria, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (G.P.); and Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine (M.G.H., W.L.L.) and Division of Biostatistics, Department of Preventive Medicine (M.N., D.M.S.), Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Denise M
authors: DM
authors: Scholtens
authors: From the Department of Paediatrics (C.J.P., N.S.M., G.P., I.A.H., C.L.A., K.K.O., D.B.D.), Medical Research Council Epidemiology Unit (K.K.O.), and Institute of Metabolic Science (D.B.D.), University of Cambridge, United Kingdom; Hospital Sant Joan de Déu, Servicio de Pediatría, Barcelona, Spain (N.S.M.); Divisão de Endocrinologia Pediátrica, Departamento de Pediatria, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (G.P.); and Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine (M.G.H., W.L.L.) and Division of Biostatistics, Department of Preventive Medicine (M.N., D.M.S.), Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Ieuan A
authors: IA
authors: Hughes
authors: From the Department of Paediatrics (C.J.P., N.S.M., G.P., I.A.H., C.L.A., K.K.O., D.B.D.), Medical Research Council Epidemiology Unit (K.K.O.), and Institute of Metabolic Science (D.B.D.), University of Cambridge, United Kingdom; Hospital Sant Joan de Déu, Servicio de Pediatría, Barcelona, Spain (N.S.M.); Divisão de Endocrinologia Pediátrica, Departamento de Pediatria, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (G.P.); and Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine (M.G.H., W.L.L.) and Division of Biostatistics, Department of Preventive Medicine (M.N., D.M.S.), Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Carlo L
authors: CL
authors: Acerini
authors: From the Department of Paediatrics (C.J.P., N.S.M., G.P., I.A.H., C.L.A., K.K.O., D.B.D.), Medical Research Council Epidemiology Unit (K.K.O.), and Institute of Metabolic Science (D.B.D.), University of Cambridge, United Kingdom; Hospital Sant Joan de Déu, Servicio de Pediatría, Barcelona, Spain (N.S.M.); Divisão de Endocrinologia Pediátrica, Departamento de Pediatria, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (G.P.); and Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine (M.G.H., W.L.L.) and Division of Biostatistics, Department of Preventive Medicine (M.N., D.M.S.), Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Ken K
authors: KK
authors: Ong
authors: From the Department of Paediatrics (C.J.P., N.S.M., G.P., I.A.H., C.L.A., K.K.O., D.B.D.), Medical Research Council Epidemiology Unit (K.K.O.), and Institute of Metabolic Science (D.B.D.), University of Cambridge, United Kingdom; Hospital Sant Joan de Déu, Servicio de Pediatría, Barcelona, Spain (N.S.M.); Divisão de Endocrinologia Pediátrica, Departamento de Pediatria, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (G.P.); and Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine (M.G.H., W.L.L.) and Division of Biostatistics, Department of Preventive Medicine (M.N., D.M.S.), Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: William L
authors: WL
authors: Lowe
authors: From the Department of Paediatrics (C.J.P., N.S.M., G.P., I.A.H., C.L.A., K.K.O., D.B.D.), Medical Research Council Epidemiology Unit (K.K.O.), and Institute of Metabolic Science (D.B.D.), University of Cambridge, United Kingdom; Hospital Sant Joan de Déu, Servicio de Pediatría, Barcelona, Spain (N.S.M.); Divisão de Endocrinologia Pediátrica, Departamento de Pediatria, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (G.P.); and Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine (M.G.H., W.L.L.) and Division of Biostatistics, Department of Preventive Medicine (M.N., D.M.S.), Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: David B
authors: DB
authors: Dunger
mesh_terms: D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D001795:Blood Pressure Determination; D002135:Calcium-Binding Proteins; D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D056726:Genetic Association Studies; D005865:Gestational Age; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000235:genetics* / Q000503:physiopathology; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D016017:Odds Ratio; D011247:Pregnancy; D011256:Pregnancy Outcome; D011257:Pregnancy Proteins / Q000235:genetics; D011446:Prospective Studies; D062085:RNA, Long Noncoding / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011257:Pregnancy Proteins; D062085:RNA, Long Noncoding
keywords: blood pressure; hypertension, pregnancy-induced; meta-analysis; placenta; preeclampsia