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No evidence of an association between mitochondrial DNA variants and osteoarthritis in 7393 cases and 5122 controls
  1. Gavin Hudson1,
  2. Kalliope Panoutsopoulou2,
  3. Ian Wilson1,
  4. Lorraine Southam2,3,
  5. Nigel W Rayner3,4,
  6. Nigel Arden5,6,
  7. Fraser Birrell7,8,
  8. Ian Carluke8,
  9. Andrew Carr6,
  10. Kay Chapman6,
  11. Panos Deloukas2,
  12. Michael Doherty9,
  13. Andrew McCaskie7,10,
  14. William E R Ollier11,
  15. Stuart H Ralston12,
  16. Mike R Reed8,
  17. Tim D Spector13,
  18. Ana M Valdes13,
  19. Gillian A Wallis14,
  20. J Mark Wilkinson15,16,
  21. Eleftheria Zeggini2,
  22. David C Samuels17,
  23. John Loughlin7,
  24. Patrick F Chinnery1 arcOGEN Consortium
  1. 1Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK
  2. 2Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
  3. 3Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
  4. 4The Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
  5. 5The MRC Epidemiology Resource Centre, University of Southampton, Southampton, UK
  6. 6The Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
  7. 7Institute of Cellular Medicine, The Medical School, Framlington Place, Newcastle upon Tyne, UK
  8. 8Northumbria Healthcare NHS Foundation Trust, Ashington, UK
  9. 9Academic Rheumatology, University of Nottingham, Nottingham, UK
  10. 10The Freeman Hospital, Newcastle upon Tyne, UK
  11. 11The Centre for Integrated Genomic Medical Research, The University of Manchester, Manchester, UK
  12. 12The Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  13. 13TwinsUK Unit, King's College London, London, UK
  14. 14The Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, UK
  15. 15The Academic Unit of Bone Metabolism, Department of Human Metabolism, University of Sheffield, Sheffield, UK
  16. 16The Sheffield NIHR Musculoskeletal Biomedical Research Unit, Northern General Hospital, Sheffield, UK
  17. 17Center for Human Genetics Research, Vanderbilt University Medical Centre, Nashville, Tennessee USA
  1. Correspondence to Professor John Loughlin, Institute of Cellular Medicine, Newcastle University, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK; John.loughlin{at} and Professor Patrick F Chinnery, Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK; P.F.Chinnery{at}


Objectives Osteoarthritis (OA) has a complex aetiology with a strong genetic component. Genome-wide association studies implicate several nuclear genes in the aetiology, but a major component of the heritability has yet to be defined at the molecular level. Initial studies implicate maternally inherited variants of mitochondrial DNA (mtDNA) in subgroups of patients with OA based on gender and specific joint involvement, but these findings have not been replicated.

Methods The authors studied 138 maternally inherited mtDNA variants genotyped in a two cohort genetic association study across a total of 7393 OA cases from the arcOGEN consortium and 5122 controls genotyped in the Wellcome Trust Case Control consortium 2 study.

Results Following data quality control we examined 48 mtDNA variants that were common in cohort 1 and cohort 2, and found no association with OA. None of the phenotypic subgroups previously associated with mtDNA haplogroups were associated in this study.

Conclusions We were not able to replicate previously published findings in the largest mtDNA association study to date. The evidence linking OA to mtDNA is not compelling at present.

  • Gene Polymorphism
  • Osteoarthritis
  • Pharmacogenetics

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