TY - JOUR
T1 - Association of mitochondrial DNA copy number with cardiometabolic diseases
AU - TOPMed mtDNA Working Group in NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
AU - Liu, Xue
AU - Longchamps, Ryan J.
AU - Wiggins, Kerri L.
AU - Raffield, Laura M.
AU - Bielak, Lawrence F.
AU - Zhao, Wei
AU - Pitsillides, Achilleas
AU - Blackwell, Thomas W.
AU - Yao, Jie
AU - Guo, Xiuqing
AU - Kurniansyah, Nuzulul
AU - Thyagarajan, Bharat
AU - Pankratz, Nathan
AU - Rich, Stephen S.
AU - Taylor, Kent D.
AU - Peyser, Patricia A.
AU - Heckbert, Susan R.
AU - Seshadri, Sudha
AU - Cupples, L. Adrienne
AU - Boerwinkle, Eric
AU - Grove, Megan L.
AU - Larson, Nicholas B.
AU - Smith, Jennifer A.
AU - Vasan, Ramachandran S.
AU - Sofer, Tamar
AU - Fitzpatrick, Annette L.
AU - Fornage, Myriam
AU - Ding, Jun
AU - Correa, Adolfo
AU - Abecasis, Goncalo
AU - Psaty, Bruce M.
AU - Wilson, James G.
AU - Levy, Daniel
AU - Rotter, Jerome I.
AU - Bis, Joshua C.
AU - Satizabal, Claudia L.
AU - Arking, Dan E.
AU - Liu, Chunyu
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2021/10/13
Y1 - 2021/10/13
N2 - 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.
AB - 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.
KW - aging
KW - cardiometabolic disease
KW - inflammation
KW - mitochondrial DNA copy number
KW - white blood cell counts
KW - whole-exom sequencing
KW - whole-genome sequencing
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U2 - 10.1016/j.xgen.2021.100006
DO - 10.1016/j.xgen.2021.100006
M3 - Article
AN - SCOPUS:85121200823
SN - 2666-979X
VL - 1
JO - Cell Genomics
JF - Cell Genomics
IS - 1
M1 - 100006
ER -
