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Title: Cardiometabolic Polygenic Risk Scores and Osteoarthritis Outcomes: A Mendelian Randomization Study Using Data From the Malmö Diet and Cancer Study and the UK Biobank.
Authors: Hindy, G
Åkesson, KE
Melander, O
Aragam, KG
Haas, ME
Nilsson, PM
Kadam, UT
Orho-Melander, M
First Published: 7-Jan-2019
Publisher: Wiley, American College of Rheumatology
Citation: Arthritis and Rheumatology, 2019, 71(6), pp. 925-934
Abstract: OBJECTIVE: To investigate the causal role of cardiometabolic risk factors in osteoarthritis (OA) using associated genetic variants. METHODS: We studied 27,691 adults from the Malmö Diet and Cancer Study (MDCS) and replicated novel findings among 376,435 adults from the UK Biobank. Trait-specific polygenic risk scores for low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels, triglyceride levels, body mass index (BMI), fasting plasma glucose (FPG) levels, and systolic blood pressure (BP) were used to test the associations of genetically predicted elevations in each trait with incident OA diagnosis (n = 3,559), OA joint replacement (n = 2,780), or both (total OA; n = 4,226) in Mendelian randomization (MR) analyses in the MDCS, and with self-reported and/or hospital-diagnosed OA (n = 65,213) in the UK Biobank. Multivariable MR, MR-Egger, and weighted median MR were used to adjust for potential pleiotropic biases. RESULTS: In the MDCS, genetically predicted elevation in LDL cholesterol level was associated with a lower risk of OA diagnosis (odds ratio [OR] 0.83 [95% confidence interval (95% CI) 0.73-0.95] per 1SD increase) and total OA (OR 0.87 [95% CI 0.78-0.98]), which was supported by multivariable MR for OA diagnosis (OR 0.84 [95% CI 0.75-0.95]) and total OA (0.87 [95% CI 0.78-0.97]), and by conventional 2-sample MR for OA diagnosis (OR 0.86 [95% CI 0.75-0.98]). MR-Egger indicated no pleiotropic bias. Genetically predicted elevation in BMI was associated with an increased risk of OA diagnosis (OR 1.65 [95% CI 1.14-2.41]), while MR-Egger indicated pleiotropic bias and a larger association with OA diagnosis (OR 3.25 [1.26-8.39]), OA joint replacement (OR 3.81 [95% CI 1.39-10.4]), and total OA (OR 3.41 [95% CI 1.43-8.15]). No associations were observed between genetically predicted HDL cholesterol level, triglyceride level, FPG level, or systolic BP and OA outcomes. The associations with LDL cholesterol levels were replicated in the UK Biobank (OR 0.95 [95% CI 0.93-0.98]). CONCLUSION: Our MR study provides evidence of a causal role of lower LDL cholesterol level and higher BMI in OA.
DOI Link: 10.1002/art.40812
eISSN: 2326-5205
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2019. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License (, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Appears in Collections:Published Articles, Dept. of Health Sciences

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