Association of mitochondrial DNA copy number with cardiometabolic diseases

TOPMed mtDNA Working Group in NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium

doi:10.1016/j.xgen.2021.100006

Association of mitochondrial DNA copy number with cardiometabolic diseases

TOPMed mtDNA Working Group in NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

Abstract

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.

Original language	English (US)
Article number	100006
Journal	Cell Genomics
Volume	1
Issue number	1
DOIs	https://doi.org/10.1016/j.xgen.2021.100006
State	Published - Oct 13 2021
Externally published	Yes

Keywords

aging
cardiometabolic disease
inflammation
mitochondrial DNA copy number
white blood cell counts
whole-exom sequencing
whole-genome sequencing

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology (miscellaneous)
Genetics

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10.1016/j.xgen.2021.100006

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@article{9b235244951a4879af732862a165eb6d,

title = "Association of mitochondrial DNA copy number with cardiometabolic diseases",

abstract = "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.",

keywords = "aging, cardiometabolic disease, inflammation, mitochondrial DNA copy number, white blood cell counts, whole-exom sequencing, whole-genome sequencing",

author = "\{TOPMed mtDNA Working Group in NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium\} and Xue Liu and Longchamps, \{Ryan J.\} and Wiggins, \{Kerri L.\} and Raffield, \{Laura M.\} and Bielak, \{Lawrence F.\} and Wei Zhao and Achilleas Pitsillides and Blackwell, \{Thomas W.\} and Jie Yao and Xiuqing Guo and Nuzulul Kurniansyah and Bharat Thyagarajan and Nathan Pankratz and Rich, \{Stephen S.\} and Taylor, \{Kent D.\} and Peyser, \{Patricia A.\} and Heckbert, \{Susan R.\} and Sudha Seshadri and Cupples, \{L. Adrienne\} and Eric Boerwinkle and Grove, \{Megan L.\} and Larson, \{Nicholas B.\} and Smith, \{Jennifer A.\} and Vasan, \{Ramachandran S.\} and Tamar Sofer and Fitzpatrick, \{Annette L.\} and Myriam Fornage and Jun Ding and Adolfo Correa and Goncalo Abecasis and Psaty, \{Bruce M.\} and Wilson, \{James G.\} and Daniel Levy and Rotter, \{Jerome I.\} and Bis, \{Joshua C.\} and Satizabal, \{Claudia L.\} and Arking, \{Dan E.\} and Chunyu Liu",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

month = oct,

day = "13",

doi = "10.1016/j.xgen.2021.100006",

language = "English (US)",

volume = "1",

journal = "Cell Genomics",

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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

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

UR - https://www.scopus.com/pages/publications/85121200823

UR - https://www.scopus.com/pages/publications/85121200823#tab=citedBy

U2 - 10.1016/j.xgen.2021.100006

DO - 10.1016/j.xgen.2021.100006

M3 - Article

C2 - 35036986

AN - SCOPUS:85121200823

SN - 2666-979X

VL - 1

JO - Cell Genomics

JF - Cell Genomics

IS - 1

M1 - 100006

ER -

Association of mitochondrial DNA copy number with cardiometabolic diseases

Abstract

Keywords

ASJC Scopus subject areas

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