학술논문
Association of mitochondrial DNA copy number with cardiometabolic diseases
Document Type
article
Author
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
Source
Cell Genomics, Vol 1, Iss 1, Pp 100006- (2021)
Subject
Language
English
ISSN
2666-979X
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.