The Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly.

Aged Aged, 80 and over Cohort Studies Databases, Genetic Female Gene Frequency Genetic Predisposition to Disease Genetic Variation Genome, Human Healthy Volunteers Humans Male Middle Aged Mitochondria / genetics Neoplasms / genetics Physical Functional Performance Polymorphism, Single Nucleotide Whole Genome Sequencing

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
23 01 2020
Historique:
received: 21 07 2019
accepted: 13 12 2019
entrez: 25 1 2020
pubmed: 25 1 2020
medline: 25 4 2020
Statut: epublish

Résumé

Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing.

Identifiants

DOI: 10.1038/s41467-019-14079-0 PMID: 31974348 PMC: PMC6978518
pubmed: 31974348
doi: 10.1038/s41467-019-14079-0
pii: 10.1038/s41467-019-14079-0
pmc: PMC6978518
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

435

Subventions

Organisme : NIA NIH HHS
ID : U19 AG062682
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG029824
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_12028
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom

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Auteurs

Mark Pinese (M)

Garvan Institute of Medical Research, Sydney, NSW, Australia.
Children's Cancer Institute, University of New South Wales, Sydney, NSW, Australia.
School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.

Paul Lacaze (P)

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
ORCID: 0000-0002-0902-6798

Emma M Rath (EM)

Garvan Institute of Medical Research, Sydney, NSW, Australia.
ORCID: 0000-0002-8430-5236

Andrew Stone (A)

Garvan Institute of Medical Research, Sydney, NSW, Australia.
Children's Cancer Institute, University of New South Wales, Sydney, NSW, Australia.
School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.

Marie-Jo Brion (MJ)

Garvan Institute of Medical Research, Sydney, NSW, Australia.

Adam Ameur (A)

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
ORCID: 0000-0001-6085-6749

Sini Nagpal (S)

Center for Integrative Genomics, Georgia Institute of Technology, Atlanta, GA, USA.

Clare Puttick (C)

Garvan Institute of Medical Research, Sydney, NSW, Australia.

Shane Husson (S)

Garvan Institute of Medical Research, Sydney, NSW, Australia.

Dmitry Degrave (D)

Garvan Institute of Medical Research, Sydney, NSW, Australia.

Tina Navin Cristina (TN)

Sax Institute, Sydney, NSW, Australia.

Vivian F S Kahl (VFS)

Children's Medical Research Institute, Faculty of Medicine and Health, University of Sydney, Westmead, NSW, Australia.

Aaron L Statham (AL)

Garvan Institute of Medical Research, Sydney, NSW, Australia.

Robyn L Woods (RL)

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

John J McNeil (JJ)

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
ORCID: 0000-0002-1049-5129

Moeen Riaz (M)

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Margo Barr (M)

Centre for Primary Health Care and Equity, University of New South Wales, Sydney, NSW, Australia.

Mark R Nelson (MR)

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.

Christopher M Reid (CM)

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
School of Public Health, Curtin University, Perth, WA, Australia.

Anne M Murray (AM)

Berman Center for Outcomes and Clinical Research, Hennepin Healthcare Research Institute, Hennepin Healthcare, Minneapolis, MN, USA.
Division of Geriatrics, Department of Medicine, Hennepin County Medical Center and University of Minnesota, Minneapolis, MN, USA.

Raj C Shah (RC)

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

Rory Wolfe (R)

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Joshua R Atkins (JR)

School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia.
Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, NSW, Australia.
ORCID: 0000-0003-0821-1112

Chantel Fitzsimmons (C)

School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia.
Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, NSW, Australia.

Heath M Cairns (HM)

School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia.
Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, NSW, Australia.

Melissa J Green (MJ)

School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
Neuroscience Research Australia, Sydney, NSW, Australia.

Vaughan J Carr (VJ)

School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
Neuroscience Research Australia, Sydney, NSW, Australia.
Department of Psychiatry, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia.

Mark J Cowley (MJ)

Garvan Institute of Medical Research, Sydney, NSW, Australia.
Children's Cancer Institute, University of New South Wales, Sydney, NSW, Australia.
School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.

Hilda A Pickett (HA)

Children's Medical Research Institute, Faculty of Medicine and Health, University of Sydney, Westmead, NSW, Australia.

Paul A James (PA)

Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
ORCID: 0000-0002-4361-4657

Joseph E Powell (JE)

UNSW Cellular Genomics Futures Institute, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, NSW, Australia.

Warren Kaplan (W)

Garvan Institute of Medical Research, Sydney, NSW, Australia.
St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.

Greg Gibson (G)

Center for Integrative Genomics, Georgia Institute of Technology, Atlanta, GA, USA.
ORCID: 0000-0002-5352-5877

Ulf Gyllensten (U)

Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Murray J Cairns (MJ)

School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia.
Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, NSW, Australia.
ORCID: 0000-0003-2490-2538

Martin McNamara (M)

Sax Institute, Sydney, NSW, Australia.

Marcel E Dinger (ME)

Garvan Institute of Medical Research, Sydney, NSW, Australia.
School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, NSW, Australia.
ORCID: 0000-0003-4423-934X

David M Thomas (DM)

Garvan Institute of Medical Research, Sydney, NSW, Australia. d.thomas@garvan.org.au.
St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia. d.thomas@garvan.org.au.
ORCID: 0000-0002-2527-5428

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › The Medical Genome Reference Bank contains...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › The Medical Genome Reference Bank contains...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › The Medical Genome Reference Bank contains...
questionsmedicales.fr › Sciences de l'information › Mémorisation et recherche des informations › Bases de données comme sujet › Bases de données factuelles › Bases de données génétiques › The Medical Genome Reference Bank contains...
questionsmedicales.fr › Phénomènes génétiques › Fréquence d'allèle › The Medical Genome Reference Bank contains...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › The Medical Genome Reference Bank contains...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › The Medical Genome Reference Bank contains...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Génome humain › The Medical Genome Reference Bank contains...
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