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Clinical and epidemiological research
Extended report
Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data
  1. Katherine S Elliott1*,
  2. Kay Chapman1,2,*,
  3. Aaron Day-Williams3,
  4. Kalliope Panoutsopoulou3,
  5. Lorraine Southam1,3,
  6. Cecilia M Lindgren1 the GIANT consortium4*,
  7. Nigel Arden5,6,
  8. Nadim Aslam7,
  9. Fraser Birrell8,9,
  10. Ian Carluke9,
  11. Andrew Carr2,4,
  12. Panos Deloukas3,
  13. Michael Doherty10,
  14. John Loughlin11,
  15. Andrew McCaskie11,12,
  16. William E R Ollier13,
  17. Ashok Rai14,
  18. Stuart Ralston15,
  19. Mike R Reed9,
  20. Timothy D Spector16,
  21. Ana M Valdes16,
  22. Gillian A Wallis17,
  23. Mark Wilkinson18,19 the arcOGEN consortium4,
  24. Eleftheria Zeggini3
  1. 1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
  2. 2Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
  3. 3Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
  4. 4NIHR Biomedical Research Unit, University of Oxford, Oxford, UK
  5. 5MRC Epidemiology Resource Centre, University of Southampton, Southampton, UK
  6. 6Orthopaedic Department, Worcestershire Acute Hospitals NHS Trust, Worcester, UK
  7. 7Musculoskeletal Research Group, Newcastle University, Institute of Cellular Medicine, The Medical School, Newcastle upon Tyne, UK
  8. 8Northumbria Healthcare NHS Foundation Trust, Wansbeck General Hospital, Ashington, UK
  9. 9Academic Rheumatology, University of Nottingham, Nottingham, UK
  10. 10Institute of Cellular Medicine, Musculoskeletal Research Group, Newcastle University, Newcastle upon Tyne, UK
  11. 11The Newcastle upon Tyne Hospitals NHS Trust Foundation Trust, The Freeman Hospital, Newcastle upon Tyne, UK
  12. 12Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK
  13. 13Rheumatology Department, Worcestershire Acute Hospitals NHS Trust, Worcester, UK
  14. 14Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  15. 15Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
  16. 16Wellcome Trust Centre for Cell Matrix Research, University of Manchester, Manchester, UK
  17. 17Academic Unit of Bone Metabolism, Department of Human Metabolism, University of Sheffield, Sheffield, UK
  18. 18Sheffield NIHR Bone Biomedical Research Unit, Centre for Biomedical Research, Northern General Hospital, Sheffield, UK
  19. 19xxxxx
  1. Correspondence to Eleftheria Zeggini, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK; eleftheria@sanger.ac.uk

Abstract

Objectives Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale.

Methods We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls.

Results We found significant overlap between osteoarthritis and height (p=3.3×10−5 for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10−5). As expected, this signal was attenuated when we adjusted for BMI.

Conclusions We found a significant excess of shared signals between both osteoarthritis and height and osteoarthritis and BMI, suggestive of a common genetic aetiology. However, only one signal showed association with osteoarthritis when followed up in a new dataset.

  • Osteoarthritis
  • Gene Polymorphism
  • Epidemiology

https://doi.org/10.1136/annrheumdis-2012-202081

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