Poster Annual Conference of the Genetics Society of Australasia with the NZ Society for Biochemistry & Molecular Biology

genome-wide association study of gout in 111,098 people of european ancestry (547)

Tanya J Major 1 , Murray J Cadzow 1 , Marilyn E Merriman 1 , Amanda J Phipps-Green 1 , Ruth KG Topless 1 , Abhishek Abhishek 2 , Mariano Andreas 3 , Linda A Bradbury 4 , Russell RC Buchanan 5 , Katie Cremin 6 , Cloe Erika de Guzman 4 , Janak R de Zoysa 7 , Michael Doherty 2 , Catherine L Hill 8 , Tom WJ Huizinga 9 , Timothy L Jansen 10 , Matthijs Janssen 11 , Leo AB Joosten 12 , Fina AS Kurreeman 9 , Susan Lester 8 , Frederic Liote 13 , Donia McCartney 14 , Hirotaka Matsuo 15 , Geraldine M McCarthy 16 , Sally PA McCormick 1 , Rinki Murphy 7 , Karel Pavelka 17 , Fernando Perez-Ruiz 18 , Juan Garcia Puig 19 , Tim RDJ Radstake 20 , Philip L Riches 21 , Maureen Rischmueller 8 , Ed Roddy 22 , Malcolm D Smith 23 , Eli A Stahl 24 , Blanka Stiburkova 17 , Richard S Stubbs 25 , Anne-Kathrin Tausche 26 , Rosa Torres Jimenez 19 , Rob J Walker 1 , Ken Yamamoto 27 , Matthew A Brown 4 , Hyon K Choi 28 , Nicola Dalbeth 7 , Alex So 29 , Lisa K Stamp 1 , Tony R Merriman 1
  1. University of Otago, Dunedin, New Zealand
  2. University of Nottingham, Nottingham, England
  3. Universidad Miguel Hernandez, Alicante, Spain
  4. Queensland University of Technology, Brisbane, Australia
  5. University of Melbourne, Melbourne, Australia
  6. University of Queensland, Brisbane, Australia
  7. University of Auckland, Auckland, New Zealand
  8. Queen Elizabeth Hospital, Adelaide, Australia
  9. Leiden University Medical Centre, Leiden, Netherlands
  10. VieCuri Medical Centre, Venlo, Netherlands
  11. Rijnstate Hospital, Arnhem, Netherlands
  12. Radboud University Medical Centre, Nijmegen, Netherlands
  13. Hospital Lariboisiere, Paris, France
  14. Environmental and Scientific Research, Wellington, New Zealand
  15. National Defence Medical College, Saitama, Japan
  16. University College Dublin, Dublin, Ireland
  17. Institute of Rheumatology, Prague, Czech Republic
  18. Hospital de Cruces, Vizcaya, Spain
  19. Hospital Uinversitario La Paz, Madrid, Spain
  20. University Medical Centre Utrecht, Utrecht, Netherlands
  21. University of Edinburgh, Edinburgh, Scotland
  22. Keele University, Newcastle, England
  23. Flinders Medical Centre and Repatriation Hospital, Adelaide, Australia
  24. Mount Sinai School of Medicine, New Your, United States of America
  25. P3 Research Limited, Wellington, New Zealand
  26. University of Dresden, Dresden, Germany
  27. Kurume University, Kurume, Japan
  28. Harvard Medical School, Boston, United States of America
  29. University of Lausanne, Lausanne, Switzerland

Background/Aims: Gout progresses through three disease stages: hyperuricaemia, monosodium urate crystal deposition, and innate immune response to crystals. Genome-wide association studies (GWAS) have provided insight into the molecular control of hyperuricaemia; however, less is known about progression from hyperuricaemia to gout. Our aim was to conduct the largest GWAS of gout (to date) in European people.

 

Methods: This study used three data-sets: EuroGout (2,242 clinically-ascertained cases; 1,302 controls), the Health Professionals Follow-Up (HPFS) and Nurses’ Health Studies (NHS) (1,038 self-ascertained cases; 1,095 controls), and UK Biobank (2,432 cases ascertained by self-report, hospital records, and/or urate-lowering therapy use; 102,989 controls). Whole-genome genotyping was performed using the Illumina CoreExome-v24 array (EuroGout), Illumina OmniExpress-v12 array (HPFS/NHS), and Affymetrix Axiom array (UK Biobank). Overlapping markers between arrays (279,939) were identified and associated with gout (adjusted for sex and age) within each data-set separately using PLINK-v1.9. An inverse-variance weighted meta-analysis was then performed per marker using meta-v4.4 within R-v3.2.3.

 

Results: Seven loci had genome-wide significant evidence for an association with gout (P<5x10-8) – ABCG2, GCKR, PDZK1, SLC2A9, SLC17A1-A4, SLC22A12, and TRIM46.

 

Conclusions: These seven loci have all been associated with serum urate levels in previous genome-wide studies. Our data emphasises the relative importance of genetic control of serum urate, compared to the genetic control of monosodium urate crystal formation or the innate immune response, in determining gout. Further analyses are required to assess whether these loci play a role in gout irrespective of their influence on serum urate levels.

 

Funding: HRCNZ