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Arthritis Rheumatol. 2019 May 16. doi: 10.1002/art.40928. [Epub ahead of print]

Causal factors for knee, hip and hand osteoarthritis: a Mendelian randomization study in the UK Biobank.

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Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
INSERM U1132, Université Paris Diderot, Université de Paris, F-75475, Paris, France.
Department of Rheumatology, Hospital Lariboisière, Assistance Publique des Hôpitaux de Paris, F-75475, Paris, France.



There is no curative treatment of osteoarthritis (OA), which is the most common form of arthritis. The objective of this study was to identify causal risk factors for knee, hip and hand OA.


Individual level data from 384,838 unrelated participants of the UK Biobank study were analysed. Mendelian randomization analyses were performed to test for causality for body mass index (BMI), bone mineral density (BMD), serum HDL-cholesterol, LDL-cholesterol, triglycerides, type 2 diabetes, systolic blood pressure (SBP), and C-reactive protein (CRP). The main outcome was OA using hospital diagnoses (all sites, n= 48,431; knee, n= 19,727; hip, n= 11,875; hand, n= 2,330).


MR analyses demonstrated a robust causal association between genetically-determined BMI and all (per SD increase, OR= 1.57 [95% CI 1.44 to 1.71]), knee and hip OA but not hand OA. Increased genetically-determined femoral neck BMD was causally associated with all (per SD increase, OR= 1.14 [95% CI 1.06 to 1.22]), knee and hip OA. Low SBP was causally associated with all OA (per SD decrease OR= 1.55 [95% CI 1.29 to 1.87]), knee and hip OA. There was no evidence of causality for the other tested metabolic factors or C-reactive protein.


BMI exerts a major causal effect on risk of OA at the weight-bearing joints but not at the hand. Evidence of causality was observed for high BMD and low SBP on all, knee and hip OA, whereas no evidence of causality was demonstrated for other metabolic factors or CRP. This article is protected by copyright. All rights reserved.


Blood pressure; Bone density; Mendelian Randomization Analysis; Osteoarthritis; Risk factors


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