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Causal Factors for Knee, Hip, and Hand Osteoarthritis: A Mendelian Randomization Study in the UK Biobank

Journal article
Authors Thomas Funck-Brentano
Maria Nethander
Sofia Moverare-Skrtic
P. Richette
Claes Ohlsson
Published in Arthritis & Rheumatology
Volume 71
Issue 10
Pages 1634-1641
ISSN 2326-5191
Publication year 2019
Published at Core Facilities, Bioinformatics
Centre for Bone and Arthritis Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 1634-1641
Language en
Keywords high bone mass, body-mass, increased prevalence, metabolic syndrome, genetic-variants, weight-loss, population, obese, inflammation, cartilage, Rheumatology
Subject categories Endocrinology, Rheumatology and Autoimmunity


Objective There is no curative treatment for osteoarthritis (OA), which is the most common form of arthritis. This study was undertaken to identify causal risk factors of knee, hip, and hand OA. Methods Individual-level data from 384,838 unrelated participants in the UK Biobank study were analyzed. Mendelian randomization (MR) analyses were performed to test for causality for body mass index (BMI), bone mineral density (BMD), serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride levels, type 2 diabetes, systolic blood pressure (BP), and C-reactive protein (CRP) levels. The primary outcome measure was OA determined using hospital diagnoses (all sites, n = 48,431; knee, n = 19,727; hip, n = 11,875; hand, n = 2,330). Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Results MR analyses demonstrated a robust causal association of genetically determined BMI with all OA (OR per SD increase 1.57 [95% CI 1.44-1.71]), and with knee OA and hip OA, but not with hand OA. Increased genetically determined femoral neck BMD was causally associated with all OA (OR per SD increase 1.14 [95% CI 1.06-1.22]), knee OA, and hip OA. Low systolic BP was causally associated with all OA (OR per SD decrease 1.55 [95% CI 1.29-1.87]), knee OA, and hip OA. There was no evidence of causality for the other tested metabolic factors or CRP level. Conclusion Our findings indicate that BMI exerts a major causal effect on the risk of OA at weight-bearing joints, but not at the hand. Evidence of causality of all OA, knee OA, and hip OA was also observed for high femoral neck BMD and low systolic BP. However, we found no evidence of causality for other metabolic factors or CRP level.

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