Rapid Fire & Poster Presentation 40th Annual Lorne Genome Conference 2019

The Medical Genome Reference Bank: Whole genomes and phenotype of 2,570 healthy elderly (#101)

Mark Pinese 1 2 , Paul Lacaze 3 , Emma M Rath 1 , Andrew Stone 1 , Marie-Jo Brion 1 , Adam Ameur 3 4 5 , Sini Nagpal 6 , Clare Puttick 1 , Shane Husson 1 , Dmitry Degrave 1 , Tina Navin Cristina 7 , Vivian F Silva Kahl 8 , Aaron L Statham 1 , Robyn L Woods 3 , John J McNeil 3 , Moeen Riaz 3 , Margo Barr 9 , Mark R Nelson 3 10 , Christopher M Reid 3 11 , Anne M Murray 12 13 , Raj C Shah 14 , Rory Wolfe 3 , Joshua R Atkins 15 16 , Chantel Fitzsimmons 15 16 , Heath M Cairns 15 16 , Melissa J Green 17 18 , Vaughan J Carr 17 18 19 , Mark J Cowley 1 2 20 , Hilda A Pickett 8 , Paul A James 21 22 , Joseph E Powell 1 2 23 , Warren Kaplan 1 2 , Greg Gibson 6 , Ulf Gyllensten 4 5 , Murray J Cairns 15 16 , Martin McNamara 7 , Marcel E Dinger 1 2 , David M Thomas 1 2
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. St Vincent's Clinical School, UNSW Australia, Sydney, NSW, Australia
  3. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia
  4. Science for Life Laboratory, Uppsala University, Uppsala, Sweden
  5. National Genomics Infrastructure, Science for Life Laboratory, Uppsala, Sweden
  6. Center for Integrative Genomics, Georgia Institute of Technology, Atlanta, USA
  7. Sax Institute, Sydney, Australia
  8. Children's Medical Research Institute, University of Sydney, Westmead, NSW, Australia
  9. Centre for Primary Health Care and Equity, University of New South Wales, Sydney, NSW, Australia
  10. Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
  11. School of Public Health, Curtin University, Perth, WA, Australia
  12. Berman Center for Outcomes and Clinical Research, Hennepin Healthcare Research Institute, Minneapolis, USA
  13. Division of Geriatrics, Department of Medicine, Hennepin County Medical Center and University of Minnesota, Minneapolis, USA
  14. Department of Family Medicine and Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, USA
  15. School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, Australia
  16. Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, NSW, Australia
  17. School of Psychiatry, University of New South Wales, Sydney, NSW, Australia
  18. Neuroscience Research Australia, Sydney, NSW, Australia
  19. Department of Psychiatry, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia
  20. Children’s Cancer Institute, University of New South Wales, Sydney, NSW, Australia
  21. Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  22. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia
  23. Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia

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 Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2,570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. The MGRB is the largest Australian whole genome sequencing cohort, and the largest resource of well elderly genomes and matched phenotype in the world.

We analysed the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. Individuals in the MGRB had fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK BioBank cohorts, consistent with risk depletion. We also identified pervasive age-related somatic changes in the MGRB, which were correlated with grip strength in men, suggesting that 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. This research has been conducted using the UK Biobank Resource under Application Number 17984.