1. TPMI Research Day Proton Rahman

2. Burden of Musculoskeletal Diseases MSDs is the second leading cause of disability Overall annual socioeconomic burden of MSD in Canada is estimated to be $22.3 billion 3% of Canada’s GDP

4. (HLA-B27) Axial SpA

5. Tag B27 SNP (rs116488202) 99.6% accurate in NL

6. Cost savings Current clinical test – The total cost per sample of direct HLA-B locus testing by PCR-SSO is $55.09 New test – The total cost per sample using TaqMan® tag-SNP genotyping assay was $4.09 – A 13.5-fold cost reduction – Will save EH 25K/year

7. Risk of axial SpA in B27 positive patients with inflammatory back pain

8. Epidemiology Clinical Gene/gene interaction Biomarker

9. Genetic Screen for Axial SpA Gene/AlleleTag-SNP HLA-B*2705rs116488202 HLA-B*3801rs2734331 HLA-B*3905rs3131382 HLA-B*3906rs9468859 HLA-B*4402rs3130501 HLA-B*4403rs12526186 HLA-B*4404rs2524180 HLA-B*4405rs2516683 HLA-B*0801rs6457374 HLA-C*0602rs887466 IL23Rrs11209026 ERAP1rs27434 IL12Brs6556416 CARD9rs10781500 CARD15rs2066845 TRAF3IP2rs33980500 TNFAIP3rs33980500 FBXL19rs10782001

10. Weighted Genetic Risk Score

11. MSK Risk Tool Chronic low back in patient less than 45 years of age

12. Consult Within 3 months Primary Care Allied Health: Screening Questionnaires for Axial SpA Community APC Assessment [Clinical, Labs, X-ray] [Biomarker sampling] High Probability IA Rheumatology Consult All consult with APC within 2 wks of primary screening Positive Screen for SpA Accelerated Rheumatologist Consult within 2 wks of referral Step 1 Primary Care Provider Screening using validated questionnaires Step 2 Assessment by Advanced Practice Clinicians (physiotherapists, chiropractors) at PCP centre Step 3 Rheumatology consult & shared-care tools Placed on regular wait list APC – Advanced Practice Clinicians: physiotherapists and chiropractors with 12 days of advanced training in IA; co-located in networked PCP communities. IA - Inflammatory Arthritis Consult and Shared Care Tools Negative Screen for SpA 10% randomly selected to consult with APC within 2 wks of primary screening Intermediate Probability IA Low Probability IA

13. MSK Risk Tool

14. Epigenetic Study of Advanced Ankylosis in Patients with Ankylosing Spondylitis

15. Baraliakos X, J Rheumatol 2009;36:997–1002 Variability in Radiographic Progression in AS

16. Multivariate Analysis: Interaction between Smoking, Epigenetics and Radiographic Progression Among smokers, low total methylation score was significantly associated with more radiographic progression β=2.01; 95%CI (0.75 to 3.26 p=0.0017) No such association was observed among non-smokers. (p=0.55)

17. Targeted therapy

18. Yuhua Zhang Zhiwei Gao Nayef Al-Ghanim Rose Ardern Donna Hackett Sean Hamilton Dianne Codner Amanda Dohey Guangju Zhai Darren O’Rielly Acknowledgements Dafna Gladman Vinod Chandran Remy Pollock Lihi Eder Nigil Haroon Robert Inman Mohammed Uddin