Causal association between subtypes of osteoarthritis and common comorbidities: A Mendelian randomisation study

Osteoarthr Cartil Open. 2023 Oct 21;5(4):100414. doi:10.1016/j.ocarto.2023.100414.eCollection 2023 Dec.


Will Thompson 1Subhashisa Swain 1 2Sizheng Steven Zhao 3Anne Kamps 4Carol Coupland 5Changfu Kuo 6Sita Bierma-Zeinstra 4Jos Runhaar 4Michael Doherty 1Weiya Zhang 1


Author information

1Academic Rheumatology, Clinical Sciences Building, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, United Kingdom.

2Nuffield Department of Primary Care Health Sciences, Radcliffe Primary Care Building, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, United Kingdom.

3Centre for Epidemiology Versus Arthritis, Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester, United Kingdom.

4Department of General Practice, Erasmus MC University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, Netherlands.

5Centre for Academic Primary Care, School of Medicine, University Park, Nottingham, NG7 2RD, United Kingdom.

6Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, 5, Fu-Hsing Street, Taoyuan, 333, Taiwan.


Objective: To investigate the causal association between Osteoarthritis (OA) and five comorbidities: depression, tiredness, multisite chronic pain, irritable bowel syndrome (IBS) and gout.

Design: This study used two-sample Mendelian Randomisation (MR). To select the OA genetic instruments, we used data from the largest recent genome-wide association study (GWAS) of OA (GO Consortium), with a focus on OA of the knee (62,497 cases, 333,557 controls), hip (35,445 cases, 316,943 controls) and hand (20,901 cases, 282,881 controls). Genetic associations for comorbidities were selected from GWAS for depression (246,363 cases, 561,190 controls), tiredness (449,019 participants), multisite chronic pain (387,649 participants), IBS (53,400 cases, 433,201 controls) and gout (6543 cases, 456,390 controls). We performed a bidirectional MR analysis using the inverse variance weighted method, for both joint specific and overall OA.

Results: Hip OA had a causal effect on multisite chronic pain (per unit change 0.02, 95% CI 0.01 to 0.04). Multisite chronic pain had a causal effect on knee (odd ratio (OR) 2.74, 95% CI 2.20 to 3.41), hip (OR 2.12, 95% CI 1.54 to 2.92), hand (OR 2.24, 95% CI 1.59 to 3.16) and overall OA (OR 2.44, 95% CI, 2.06 to 2.86). In addition, depression and tiredness had causal effects on knee and hand, but not hip, OA.

Conclusions: Apart from Hip OA to multisite chronic pain, other joint OA did not have causal effects on these comorbidities. In contrast, multisite chronic pain had a causal effect on any painful OA.

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