Genome-wide analysis of mitochondrial DNA copy number reveals loci implicated in nucleotide metabolism, platelet activation, and megakaryocyte proliferation.

Aged Cell Proliferation DNA Copy Number Variations DNA, Mitochondrial Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Megakaryocytes / physiology Middle Aged Mitochondria / genetics Nucleotides / metabolism Phenotype Platelet Activation Polymorphism, Single Nucleotide

Journal

Human genetics
ISSN: 1432-1203
Titre abrégé: Hum Genet
Pays: Germany
ID NLM: 7613873

Informations de publication

Date de publication:
Jan 2022
Historique:
received: 23 09 2021
accepted: 22 10 2021
pubmed: 4 12 2021
medline: 22 1 2022
entrez: 3 12 2021
Statut: ppublish

Résumé

Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses was used to prioritize genes within each of the 133 independent sites. Putative causal genes were enriched for known mitochondrial DNA depletion syndromes (p = 3.09 × 10

Identifiants

DOI: 10.1007/s00439-021-02394-w PMID: 34859289 PMC: PMC8758627
pubmed: 34859289
doi: 10.1007/s00439-021-02394-w
pii: 10.1007/s00439-021-02394-w
pmc: PMC8758627
doi:

Substances chimiques

DNA, Mitochondrial 0
Nucleotides 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

127-146

Subventions

Organisme : Medical Research Council
ID : MC_PC_19009
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH100027
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01HL144569
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG063893
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL131573
Pays : United States
Organisme : Medical Research Council
ID : MR/K002767/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01HL13573
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/4
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL144569
Pays : United States
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom

Informations de copyright

© 2021. The Author(s).

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Auteurs

R J Longchamps (RJ)

Department of Genetic Medicine, McKusick-Nathans Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

S Y Yang (SY)

Department of Genetic Medicine, McKusick-Nathans Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
ORCID: 0000-0002-6327-0847

C A Castellani (CA)

Department of Genetic Medicine, McKusick-Nathans Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada.

W Shi (W)

Department of Genetic Medicine, McKusick-Nathans Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

J Lane (J)

Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA.

M L Grove (ML)

Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, TX, USA.

T M Bartz (TM)

Cardiovascular Health Research Unit, Departments of Medicine and Biostatistics, University of Washington, Seattle, WA, USA.

C Sarnowski (C)

Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.

C Liu (C)

Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.

K Burrows (K)

MRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.

A L Guyatt (AL)

Department of Health Sciences, University of Leicester, University Road, Leicester, UK.

T R Gaunt (TR)

MRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.

T Kacprowski (T)

Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
Data Science in Biomedicine, Peter L. Reichertz Institute for Medical Informatics, TU Braunschweig and Hannover Medical School, Brunswick, Germany.

J Yang (J)

Rush Alzheimer's Disease Center and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.

P L De Jager (PL)

Center for Translational and Systems Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, USA.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.

L Yu (L)

Rush Alzheimer's Disease Center and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.

A Bergman (A)

Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY, USA.

R Xia (R)

Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.

M Fornage (M)

Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, USA.

M F Feitosa (MF)

Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, USA.

M K Wojczynski (MK)

Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, USA.

A T Kraja (AT)

Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, USA.

M A Province (MA)

Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, USA.

N Amin (N)

Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

F Rivadeneira (F)

Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

H Tiemeier (H)

Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Department of Social and Behavioral Science, Harvard T.H. School of Public Health, Boston, USA.

A G Uitterlinden (AG)

Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

L Broer (L)

Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

J B J Van Meurs (JBJ)

Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

C M Van Duijn (CM)

Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

L M Raffield (LM)

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

L Lange (L)

Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.

S S Rich (SS)

Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.

R N Lemaitre (RN)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.

M O Goodarzi (MO)

Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

C M Sitlani (CM)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.

A C Y Mak (ACY)

Cardiovascular Research Institute and Institute for Human Genetics, University of California, San Francisco, CA, USA.

D A Bennett (DA)

Rush Alzheimer's Disease Center and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.

S Rodriguez (S)

MRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.

J M Murabito (JM)

Boston University School of Medicine, Boston University, Boston, MA, USA.

K L Lunetta (KL)

Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.

N Sotoodehnia (N)

Cardiovascular Health Research Unit, Division of Cardiology, University of Washington, Seattle, WA, USA.

G Atzmon (G)

Department of Natural Science, University of Haifa, Haifa, Israel.
Departments of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.

K Ye (K)

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.

N Barzilai (N)

Departments of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.

J A Brody (JA)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.

B M Psaty (BM)

Cardiovascular Health Research Unit, Departments of Epidemiology, Medicine and Health Services, University of Washington, Seattle, WA, USA.

K D Taylor (KD)

The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.

J I Rotter (JI)

The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.

E Boerwinkle (E)

Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Baylor College of Medicine, Human Genome Sequencing Center, Houston, TX, USA.

N Pankratz (N)

Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA.

D E Arking (DE)

Department of Genetic Medicine, McKusick-Nathans Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. arking@jhmi.edu.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Genome-wide analysis of mitochondrial DNA copy...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Genome-wide analysis of mitochondrial DNA copy...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Variations de nombre de copies de segment d'ADN › Genome-wide analysis of mitochondrial DNA copy...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › ADN mitochondrial › Genome-wide analysis of mitochondrial DNA copy...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Genome-wide analysis of mitochondrial DNA copy...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genome-wide analysis of mitochondrial DNA copy...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genome-wide analysis of mitochondrial DNA copy...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Mégacaryocytes › Genome-wide analysis of mitochondrial DNA copy...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Genome-wide analysis of mitochondrial DNA copy...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › Genome-wide analysis of mitochondrial DNA copy...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Genome-wide analysis of mitochondrial DNA copy...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Genome-wide analysis of mitochondrial DNA copy...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hémostase › Activation plaquettaire › Genome-wide analysis of mitochondrial DNA copy...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Genome-wide analysis of mitochondrial DNA copy...