Association of mitochondrial DNA copy number with cardiometabolic diseases

Cell Genomics

Goncalo Abecasis¹  Eric Boerwinkle²  Dan E. Arking³  L. Adrienne Cupples⁴  Jennifer A. Smith⁵  Jun Ding⁶  Susan R. Heckbert⁷  Kerri L. Wiggins⁸  Claudia L. Satizabal⁸  James G. Wilson⁹  Megan L. Grove^1,10  Xue Liu^1,10  Achilleas Pitsillides^1,10  Nathan Pankratz^1,11  Lawrence F. Bielak^1,12  Patricia A. Peyser^1,12  Wei Zhao^1,12  Annette L. Fitzpatrick^1,12  Laura M. Raffield^1,13  Bharat Thyagarajan^1,14  Jerome I. Rotter^1,15  Chunyu Liu^1,16  Stephen S. Rich^1,17  Bruce M. Psaty^1,18  Nuzulul Kurniansyah^1,19  Adolfo Correa^1,19  Myriam Fornage^2,20  Sudha Seshadri^2,21  Nicholas B. Larson^2,22  Ramachandran S. Vasan^2,22  Daniel Levy^2,23  Tamar Sofer^2,24  Ryan J. Longchamps^2,25  Joshua C. Bis^2,26  Thomas W. Blackwell^2,26  Kent D. Taylor^2,27  Xiuqing Guo^2,27  Jie Yao^2,27 

[1] Department of Medicine, Harvard Medical School, Boston, MA 02115, USA;Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA;Departments of Epidemiology, and Health Services, University of Washington, Seattle, WA 98101, USA;Framingham Heart Study, NHLBI/NIH, Framingham, MA 01702, USA;Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA;Sections of Preventive Medicine and Epidemiology, and Cardiovascular Medicine, Boston University School of Medicine, Boston, MA 02118, USA;Cardiovascular Health Research Unit and Department of Epidemiology, University of Washington, Seattle, WA 98101, USA;Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA;Center for Human Genetics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA;Department of Biostatistics, School of Public Health, Boston University, Boston, MA 02118, USA;Department of Computational Pathology, University of Minnesota, Minneapolis, MN 55455, USA;Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA;Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA;Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA;Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA;Department of Public Health Services, Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA;Departments of Family Medicine, Epidemiology, and Global Health, University of Washington, Seattle, WA 98195, USA;Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA 02115, USA;Framingham Heart Study, NHLBI/NIH, Framingham, MA 01702, USA;Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA;Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, the University of Texas Health Science Center at Houston, Houston, TX 77030, USA;Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA;Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA;McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;TOPMed Informatics Research Center, University of Michigan, Ann Arbor, MI 48109, USA;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;

关键词: mitochondrial DNA copy number;    cardiometabolic disease;    whole-genome sequencing;    whole-exom sequencing;    aging;    white blood cell counts;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown