Cell Genomics (Oct 2021)
Association of mitochondrial DNA copy number with cardiometabolic diseases
- Xue Liu,
- Ryan J. Longchamps,
- Kerri L. Wiggins,
- Laura M. Raffield,
- Lawrence F. Bielak,
- Wei Zhao,
- Achilleas Pitsillides,
- Thomas W. Blackwell,
- Jie Yao,
- Xiuqing Guo,
- Nuzulul Kurniansyah,
- Bharat Thyagarajan,
- Nathan Pankratz,
- Stephen S. Rich,
- Kent D. Taylor,
- Patricia A. Peyser,
- Susan R. Heckbert,
- Sudha Seshadri,
- L. Adrienne Cupples,
- Eric Boerwinkle,
- Megan L. Grove,
- Nicholas B. Larson,
- Jennifer A. Smith,
- Ramachandran S. Vasan,
- Tamar Sofer,
- Annette L. Fitzpatrick,
- Myriam Fornage,
- Jun Ding,
- Adolfo Correa,
- Goncalo Abecasis,
- Bruce M. Psaty,
- James G. Wilson,
- Daniel Levy,
- Jerome I. Rotter,
- Joshua C. Bis,
- Claudia L. Satizabal,
- Dan E. Arking,
- Chunyu Liu
Affiliations
- Xue Liu
- Department of Biostatistics, School of Public Health, Boston University, Boston, MA 02118, USA
- Ryan J. Longchamps
- McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Kerri L. Wiggins
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA
- Laura M. Raffield
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Lawrence F. Bielak
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
- Wei Zhao
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
- Achilleas Pitsillides
- Department of Biostatistics, School of Public Health, Boston University, Boston, MA 02118, USA
- Thomas W. Blackwell
- TOPMed Informatics Research Center, University of Michigan, Ann Arbor, MI 48109, USA
- Jie Yao
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA
- Xiuqing Guo
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA
- Nuzulul Kurniansyah
- Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA 02115, USA
- Bharat Thyagarajan
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
- Nathan Pankratz
- Department of Computational Pathology, University of Minnesota, Minneapolis, MN 55455, USA
- Stephen S. Rich
- Department of Public Health Services, Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA
- Kent D. Taylor
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA
- Patricia A. Peyser
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
- Susan R. Heckbert
- Cardiovascular Health Research Unit and Department of Epidemiology, University of Washington, Seattle, WA 98101, USA
- Sudha Seshadri
- Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Framingham Heart Study, NHLBI/NIH, Framingham, MA 01702, USA; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA
- L. Adrienne Cupples
- Department of Biostatistics, School of Public Health, Boston University, Boston, MA 02118, USA
- Eric Boerwinkle
- Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, the University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA
- Megan L. Grove
- Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, the University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- Nicholas B. Larson
- Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA
- Jennifer A. Smith
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
- Ramachandran S. Vasan
- Framingham Heart Study, NHLBI/NIH, Framingham, MA 01702, USA; Sections of Preventive Medicine and Epidemiology, and Cardiovascular Medicine, Boston University School of Medicine, Boston, MA 02118, USA
- Tamar Sofer
- Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
- Annette L. Fitzpatrick
- Departments of Family Medicine, Epidemiology, and Global Health, University of Washington, Seattle, WA 98195, USA
- Myriam Fornage
- Center for Human Genetics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- Jun Ding
- Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA
- Adolfo Correa
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA
- Goncalo Abecasis
- TOPMed Informatics Research Center, University of Michigan, Ann Arbor, MI 48109, USA
- Bruce M. Psaty
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA; Departments of Epidemiology, and Health Services, University of Washington, Seattle, WA 98101, USA
- James G. Wilson
- Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA
- Daniel Levy
- Framingham Heart Study, NHLBI/NIH, Framingham, MA 01702, USA; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
- Jerome I. Rotter
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA
- Joshua C. Bis
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA
- Claudia L. Satizabal
- Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Framingham Heart Study, NHLBI/NIH, Framingham, MA 01702, USA; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA
- Dan E. Arking
- McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Chunyu Liu
- Department of Biostatistics, School of Public Health, Boston University, Boston, MA 02118, USA; Framingham Heart Study, NHLBI/NIH, Framingham, MA 01702, USA; Corresponding author
- Journal volume & issue
-
Vol. 1,
no. 1
p. 100006
Abstract
Summary: Mitochondrial DNA (mtDNA) is present in multiple copies in human cells. We evaluated cross-sectional associations of whole-blood mtDNA copy number (CN) with several cardiometabolic disease traits in 408,361 participants of multiple ancestries in TOPMed and UK Biobank. Age showed a threshold association with mtDNA CN: each additional 10 years of age was associated with a 0.03 SD higher level of mtDNA CN (p = 0.0014) among younger participants (younger than 65 years) versus a 0.14 SD lower level of mtDNA CN (p = 1.82 × 10−13) among older participants (65 years and older). At lower mtDNA CN levels, we found age-independent associations with increased odds of obesity (p = 5.6 × 10−238), hypertension (p = 2.8 × 10−50), diabetes (p = 3.6 × 10−7), and hyperlipidemia (p = 6.3 × 10−56). The observed decline in mtDNA CN after 65 years of age may be a key to understanding age-related diseases.
