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Epigenome-wide association study of mitochondrial genome copy number.
Wang, Penglong; Castellani, Christina A; Yao, Jie; Huan, Tianxiao; Bielak, Lawrence F; Zhao, Wei; Haessler, Jeffrey; Joehanes, Roby; Sun, Xianbang; Guo, Xiuqing; Longchamps, Ryan J; Manson, JoAnn E; Grove, Megan L; Bressler, Jan; Taylor, Kent D; Lappalainen, Tuuli; Kasela, Silva; Van Den Berg, David J; Hou, Lifang; Reiner, Alexander; Liu, Yongmei; Boerwinkle, Eric; Smith, Jennifer A; Peyser, Patricia A; Fornage, Myriam; Rich, Stephen S; Rotter, Jerome I; Kooperberg, Charles; Arking, Dan E; Levy, Daniel; Liu, Chunyu.
Afiliación
  • Wang P; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Castellani CA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Yao J; Department of Pathology and Laboratory Medicine, Western University, London, Ontario N6A 5C1, Canada.
  • Huan T; Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
  • Bielak LF; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Zhao W; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
  • Haessler J; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
  • Joehanes R; Division of Public Health Science, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Sun X; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Guo X; Department of Biostatistics, Boston University, Boston, MA 02118, USA.
  • Longchamps RJ; Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
  • Manson JE; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Grove ML; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
  • Bressler J; Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Taylor KD; Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Lappalainen T; Department of Pathology and Laboratory Medicine, Western University, London, Ontario N6A 5C1, Canada.
  • Kasela S; New York Genome Center, New York, NY 10013, USA.
  • Van Den Berg DJ; Department of Systems Biology, Columbia University, New York, NY 10034, USA.
  • Hou L; New York Genome Center, New York, NY 10013, USA.
  • Reiner A; Department of Systems Biology, Columbia University, New York, NY 10034, USA.
  • Liu Y; Department of Population and Public Health Sciences, Center for Genetic Epidemiology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA.
  • Boerwinkle E; Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
  • Smith JA; Division of Public Health Science, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Peyser PA; Department of Medicine, Divisions of Cardiology and Neurology, Duke University Medical Center, Durham, NC 27704, USA.
  • Fornage M; Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Rich SS; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Rotter JI; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
  • Kooperberg C; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
  • Arking DE; Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Levy D; Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Liu C; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22903, USA.
Hum Mol Genet ; 31(2): 309-319, 2021 12 27.
Article en En | MEDLINE | ID: mdl-34415308
We conducted cohort- and race-specific epigenome-wide association analyses of mitochondrial deoxyribonucleic acid (mtDNA) copy number (mtDNA CN) measured in whole blood from participants of African and European origins in five cohorts (n = 6182, mean age = 57-67 years, 65% women). In the meta-analysis of all the participants, we discovered 21 mtDNA CN-associated DNA methylation sites (CpG) (P < 1 × 10-7), with a 0.7-3.0 standard deviation increase (3 CpGs) or decrease (18 CpGs) in mtDNA CN corresponding to a 1% increase in DNA methylation. Several significant CpGs have been reported to be associated with at least two risk factors (e.g. chronological age or smoking) for cardiovascular disease (CVD). Five genes [PR/SET domain 16, nuclear receptor subfamily 1 group H member 3 (NR1H3), DNA repair protein, DNA polymerase kappa and decaprenyl-diphosphate synthase subunit 2], which harbor nine significant CpGs, are known to be involved in mitochondrial biosynthesis and functions. For example, NR1H3 encodes a transcription factor that is differentially expressed during an adipose tissue transition. The methylation level of cg09548275 in NR1H3 was negatively associated with mtDNA CN (effect size = -1.71, P = 4 × 10-8) and was positively associated with the NR1H3 expression level (effect size = 0.43, P = 0.0003), which indicates that the methylation level in NR1H3 may underlie the relationship between mtDNA CN, the NR1H3 transcription factor and energy expenditure. In summary, the study results suggest that mtDNA CN variation in whole blood is associated with DNA methylation levels in genes that are involved in a wide range of mitochondrial activities. These findings will help reveal molecular mechanisms between mtDNA CN and CVD.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Genoma Mitocondrial / Epigenoma Tipo de estudio: Risk_factors_studies / Systematic_reviews Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Genoma Mitocondrial / Epigenoma Tipo de estudio: Risk_factors_studies / Systematic_reviews Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos