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Identification, Heritability, and Relation With Gene Expression of Novel DNA Methylation Loci for Blood Pressure.
Huang, Yisong; Ollikainen, Miina; Muniandy, Maheswary; Zhang, Tao; van Dongen, Jenny; Hao, Guang; van der Most, Peter J; Pan, Yue; Pervjakova, Natalia; Sun, Yan V; Hui, Qin; Lahti, Jari; Fraszczyk, Eliza; Lu, Xueling; Sun, Dianjianyi; Richard, Melissa A; Willemsen, Gonneke; Heikkila, Kauko; Mateo Leach, Irene; Mononen, Nina; Kähönen, Mika; Hurme, Mikko A; Raitakari, Olli T; Drake, Amanda J; Perola, Markus; Nuotio, Marja-Liisa; Huang, Yunfeng; Khulan, Batbayar; Räikkönen, Katri; Wolffenbuttel, Bruce H R; Zhernakova, Alexandra; Fu, Jingyuan; Zhu, Haidong; Dong, Yanbin; van Vliet-Ostaptchouk, Jana V; Franke, Lude; Eriksson, Johan G; Fornage, Myriam; Milani, Lili; Lehtimäki, Terho; Vaccarino, Viola; Boomsma, Dorret I; van der Harst, Pim; de Geus, Eco J C; Salomaa, Veikko; Li, Shengxu; Chen, Wei; Su, Shaoyong; Wilson, James; Snieder, Harold.
Afiliação
  • Huang Y; From the Georgia Prevention Institute, Medical College of Georgia, Augusta University (Y. Huang, G.H., Y.P., H.Z., Y.D., S.S., X.W.).
  • Ollikainen M; Institute for Molecular Medicine FIMM, HiLIFE (M.O., M.M., K.H., J.K.), University of Helsinki, Finland.
  • Muniandy M; Department of Public Health, Faculty of Medicine (M.O., J.K.), University of Helsinki, Finland.
  • Zhang T; Institute for Molecular Medicine FIMM, HiLIFE (M.O., M.M., K.H., J.K.), University of Helsinki, Finland.
  • van Dongen J; Department of Biostatistics, Shandong University School of Public Health, Jinan, China (T.Z.).
  • Hao G; Department of Biological Psychology, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, The Netherlands (J.v.D., G.W., D.I.B., E.J.C.d.G.).
  • van der Most PJ; From the Georgia Prevention Institute, Medical College of Georgia, Augusta University (Y. Huang, G.H., Y.P., H.Z., Y.D., S.S., X.W.).
  • Pan Y; Department of Epidemiology (P.J.v.d.M., E.F., X.L., J.V.v.V.-O., H.S.), University Medical Center Groningen, University of Groningen, The Netherlands.
  • Pervjakova N; From the Georgia Prevention Institute, Medical College of Georgia, Augusta University (Y. Huang, G.H., Y.P., H.Z., Y.D., S.S., X.W.).
  • Sun YV; Estonian Genome Center, Institute of Genomics, University of Tartu, Estonia (N.P., L.M.).
  • Hui Q; Department of Epidemiology, Emory Rollins School of Public Health, Emory University, Atlanta (Y.V.S., Q.H., Y. Huang, V.V.).
  • Lahti J; Department of Epidemiology, Emory Rollins School of Public Health, Emory University, Atlanta (Y.V.S., Q.H., Y. Huang, V.V.).
  • Fraszczyk E; Turku Institute for Advanced Studies (J.L.), University of Turku, Finland.
  • Lu X; Department of Psychology and Logopedics, University of Helsinki, Finland (J.L., K.R.).
  • Sun D; Department of Epidemiology (P.J.v.d.M., E.F., X.L., J.V.v.V.-O., H.S.), University Medical Center Groningen, University of Groningen, The Netherlands.
  • Richard MA; Department of Epidemiology (P.J.v.d.M., E.F., X.L., J.V.v.V.-O., H.S.), University Medical Center Groningen, University of Groningen, The Netherlands.
  • Willemsen G; Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Guangdong, China (X.L.).
  • Heikkila K; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (D.S., W.C.).
  • Mateo Leach I; Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (D.S.).
  • Mononen N; Department of Pediatrics, Section of Hematology/Oncology, Baylor College of Medicine (M.A.R.).
  • Kähönen M; Department of Biological Psychology, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, The Netherlands (J.v.D., G.W., D.I.B., E.J.C.d.G.).
  • Hurme MA; Institute for Molecular Medicine FIMM, HiLIFE (M.O., M.M., K.H., J.K.), University of Helsinki, Finland.
  • Raitakari OT; Department of Cardiology (I.M.L., P.v.d.H.), University Medical Center Groningen, University of Groningen, The Netherlands.
  • Drake AJ; Department of Clinical Chemistry, Finnish Cardiovascular Research Center-Tampere (N.M., T.L.), Faculty of Medicine and Health Technology, Tampere University, Finland.
  • Perola M; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland (N.M., T.L.).
  • Nuotio ML; Department of Clinical Physiology, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology (M.K.), Faculty of Medicine and Health Technology, Tampere University, Finland.
  • Huang Y; Department of Microbiology and Immunology (M.A.H.), Faculty of Medicine and Health Technology, Tampere University, Finland.
  • Khulan B; Research Centre of Applied and Preventive Cardiovascular Medicine (O.T.R.), University of Turku, Finland.
  • Räikkönen K; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Finland (O.T.R.).
  • Wolffenbuttel BHR; University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, United Kingdom (A.J.D., B.K.).
  • Zhernakova A; National Institute for Health and Welfare, Helsinki, Finland (M.P., M.-L.N., V.S.).
  • Fu J; National Institute for Health and Welfare, Helsinki, Finland (M.P., M.-L.N., V.S.).
  • Zhu H; Department of Epidemiology, Emory Rollins School of Public Health, Emory University, Atlanta (Y.V.S., Q.H., Y. Huang, V.V.).
  • Dong Y; University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, United Kingdom (A.J.D., B.K.).
  • van Vliet-Ostaptchouk JV; Department of Psychology and Logopedics, University of Helsinki, Finland (J.L., K.R.).
  • Franke L; Department of Endocrinology (B.H.R.W., J.V.v.V.-O.), University Medical Center Groningen, University of Groningen, The Netherlands.
  • Eriksson JG; Department of Genetics (A.Z., J.F., L.F.), University Medical Center Groningen, University of Groningen, The Netherlands.
  • Fornage M; Department of Genetics (A.Z., J.F., L.F.), University Medical Center Groningen, University of Groningen, The Netherlands.
  • Milani L; Department of Pediatrics (J.F.), University Medical Center Groningen, University of Groningen, The Netherlands.
  • Lehtimäki T; From the Georgia Prevention Institute, Medical College of Georgia, Augusta University (Y. Huang, G.H., Y.P., H.Z., Y.D., S.S., X.W.).
  • Vaccarino V; From the Georgia Prevention Institute, Medical College of Georgia, Augusta University (Y. Huang, G.H., Y.P., H.Z., Y.D., S.S., X.W.).
  • Boomsma DI; Department of Epidemiology (P.J.v.d.M., E.F., X.L., J.V.v.V.-O., H.S.), University Medical Center Groningen, University of Groningen, The Netherlands.
  • van der Harst P; Department of Endocrinology (B.H.R.W., J.V.v.V.-O.), University Medical Center Groningen, University of Groningen, The Netherlands.
  • de Geus EJC; Department of Genetics, Genomics Coordination Center (J.V.v.V.-O.), University Medical Center Groningen, University of Groningen, The Netherlands.
  • Salomaa V; Department of Genetics (A.Z., J.F., L.F.), University Medical Center Groningen, University of Groningen, The Netherlands.
  • Li S; Department of General Practice and Primary health Care, University of Helsinki, Finland and Helsinki University Hospital, Unit of General Practice, Finland (J.G.E.).
  • Chen W; Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore (J.G.E.).
  • Su S; Brown Foundation Institute of Molecular Medicine, Mc Govern Medical School, University of Texas Health Science Center at Houston (M.F.).
  • Wilson J; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston (M.F.).
  • Snieder H; Estonian Genome Center, Institute of Genomics, University of Tartu, Estonia (N.P., L.M.).
Hypertension ; 76(1): 195-205, 2020 07.
Article em En | MEDLINE | ID: mdl-32520614
We conducted an epigenome-wide association study meta-analysis on blood pressure (BP) in 4820 individuals of European and African ancestry aged 14 to 69. Genome-wide DNA methylation data from peripheral leukocytes were obtained using the Infinium Human Methylation 450k BeadChip. The epigenome-wide association study meta-analysis identified 39 BP-related CpG sites with P<1×10-5. In silico replication in the CHARGE consortium of 17 010 individuals validated 16 of these CpG sites. Out of the 16 CpG sites, 13 showed novel association with BP. Conversely, out of the 126 CpG sites identified as being associated (P<1×10-7) with BP in the CHARGE consortium, 21 were replicated in the current study. Methylation levels of all the 34 CpG sites that were cross-validated by the current study and the CHARGE consortium were heritable and 6 showed association with gene expression. Furthermore, 9 CpG sites also showed association with BP with P<0.05 and consistent direction of the effect in the meta-analysis of the Finnish Twin Cohort (199 twin pairs and 4 singletons; 61% monozygous) and the Netherlands Twin Register (266 twin pairs and 62 singletons; 84% monozygous). Bivariate quantitative genetic modeling of the twin data showed that a majority of the phenotypic correlations between methylation levels of these CpG sites and BP could be explained by shared unique environmental rather than genetic factors, with 100% of the correlations of systolic BP with cg19693031 (TXNIP) and cg00716257 (JDP2) determined by environmental effects acting on both systolic BP and methylation levels.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pressão Sanguínea / Ilhas de CpG / Metilação de DNA / Estudo de Associação Genômica Ampla / Interação Gene-Ambiente / Hipertensão Essencial / Epigenoma Tipo de estudo: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Hypertension Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pressão Sanguínea / Ilhas de CpG / Metilação de DNA / Estudo de Associação Genômica Ampla / Interação Gene-Ambiente / Hipertensão Essencial / Epigenoma Tipo de estudo: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Hypertension Ano de publicação: 2020 Tipo de documento: Article