dc.contributor.author | Hartley, April | |
dc.contributor.author | Sanderson, Eleanor | |
dc.contributor.author | Granell, Raquel | |
dc.contributor.author | Paternoster, Lavinia | |
dc.contributor.author | Zheng, Jie | |
dc.contributor.author | Smith, George Davey | |
dc.contributor.author | Southam, Lorraine | |
dc.contributor.author | Hatzikotoulas, Konstantinos | |
dc.contributor.author | Boer, Cindy G. | |
dc.contributor.author | Van Meurs, Joyce | |
dc.contributor.author | Zeggini, Eleftheria | |
dc.contributor.author | Gregson, Celia L. | |
dc.contributor.author | Tobias, Jon H. | |
dc.contributor.author | Stefánsdóttir, Lilja | |
dc.contributor.author | Zhang, Yanfei | |
dc.contributor.author | De Almeida, Rodrigo Coutinho | |
dc.contributor.author | Wu, Tian T. | |
dc.contributor.author | Teder-Laving, Maris | |
dc.contributor.author | Skogholt, Anne Heidi | |
dc.contributor.author | Terao, Chikashi | |
dc.contributor.author | Zengini, Eleni | |
dc.contributor.author | Alexiadis, George | |
dc.contributor.author | Barysenka, Andrei | |
dc.contributor.author | Bjornsdottir, Gyda | |
dc.contributor.author | Gabrielsen, Maiken Elvestad | |
dc.contributor.author | Gilly, Arthur | |
dc.contributor.author | Ingvarsson, Thorvaldur | |
dc.contributor.author | Johnsen, Marianne Bakke | |
dc.contributor.author | Jonsson, Helgi Freyr | |
dc.contributor.author | Kloppenburg, Margreet G. | |
dc.contributor.author | Luetge, Almut | |
dc.contributor.author | Mägi, Reedik | |
dc.contributor.author | Mangino, Massimo | |
dc.contributor.author | Nelissen, Rob R.G.H.H. | |
dc.contributor.author | Shivakumar, Manu | |
dc.contributor.author | Steinberg, Julia | |
dc.contributor.author | Takuwa, Hiroshi | |
dc.contributor.author | Thomas, Laurent | |
dc.contributor.author | Tuerlings, Margo | |
dc.contributor.author | Babis, George | |
dc.contributor.author | Cheung, Jason Pui Yin | |
dc.contributor.author | Samartzis, Dino | |
dc.contributor.author | Lietman, Steve A. | |
dc.contributor.author | Slagboom, P. Eline | |
dc.contributor.author | Stefansson, Kari | |
dc.contributor.author | Uitterlinden, André G. | |
dc.contributor.author | Winsvold, Bendik K S | |
dc.contributor.author | Zwart, John Anker Henrik | |
dc.contributor.author | Sham, Pak Chung | |
dc.contributor.author | Thorleifsson, Gudmar | |
dc.contributor.author | Gaunt, Tom R. | |
dc.contributor.author | Morris, Andrew P. | |
dc.contributor.author | Valdes, Ana M. | |
dc.contributor.author | Tsezou, Aspasia | |
dc.contributor.author | Cheah, Kathryn S.E. | |
dc.contributor.author | Ikegawa, Shiro | |
dc.contributor.author | Hveem, Kristian | |
dc.contributor.author | Esko, Tõnu | |
dc.contributor.author | Wilkinson, J. Mark | |
dc.contributor.author | Meulenbelt, Ingrid | |
dc.contributor.author | Michael Lee, Ming Ta | |
dc.contributor.author | Styrkársdóttir, Unnur | |
dc.date.accessioned | 2023-05-19T07:49:49Z | |
dc.date.available | 2023-05-19T07:49:49Z | |
dc.date.created | 2022-11-01T13:40:27Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | International Journal of Epidemiology. 2022, 51 (4), 1254-1267. | en_US |
dc.identifier.issn | 0300-5771 | |
dc.identifier.uri | https://hdl.handle.net/11250/3068284 | |
dc.description.abstract | Objectives
Observational analyses suggest that high bone mineral density (BMD) is a risk factor for osteoarthritis (OA); it is unclear whether this represents a causal effect or shared aetiology and whether these relationships are body mass index (BMI)-independent. We performed bidirectional Mendelian randomization (MR) to uncover the causal pathways between BMD, BMI and OA.
Methods
One-sample (1S)MR estimates were generated by two-stage least-squares regression. Unweighted allele scores instrumented each exposure. Two-sample (2S)MR estimates were generated using inverse-variance weighted random-effects meta-analysis. Multivariable MR (MVMR), including BMD and BMI instruments in the same model, determined the BMI-independent causal pathway from BMD to OA. Latent causal variable (LCV) analysis, using weight-adjusted femoral neck (FN)–BMD and hip/knee OA summary statistics, determined whether genetic correlation explained the causal effect of BMD on OA.
Results
1SMR provided strong evidence for a causal effect of BMD estimated from heel ultrasound (eBMD) on hip and knee OA {odds ratio [OR]hip = 1.28 [95% confidence interval (CI) = 1.05, 1.57], p = 0.02, ORknee = 1.40 [95% CI = 1.20, 1.63], p = 3 × 10–5, OR per standard deviation [SD] increase}. 2SMR effect sizes were consistent in direction. Results suggested that the causal pathways between eBMD and OA were bidirectional (βhip = 1.10 [95% CI = 0.36, 1.84], p = 0.003, βknee = 4.16 [95% CI = 2.74, 5.57], p = 8 × 10–9, β = SD increase per doubling in risk). MVMR identified a BMI-independent causal pathway between eBMD and hip/knee OA. LCV suggested that genetic correlation (i.e. shared genetic aetiology) did not fully explain the causal effects of BMD on hip/knee OA.
Conclusions
These results provide evidence for a BMI-independent causal effect of eBMD on OA. Despite evidence of bidirectional effects, the effect of BMD on OA did not appear to be fully explained by shared genetic aetiology, suggesting a direct action of bone on joint deterioration. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Oxford University Press | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Using multivariable Mendelian randomization to estimate the causal effect of bone mineral density on osteoarthritis risk, independently of body mass index | en_US |
dc.title.alternative | Using multivariable Mendelian randomization to estimate the causal effect of bone mineral density on osteoarthritis risk, independently of body mass index | en_US |
dc.type | Peer reviewed | en_US |
dc.type | Journal article | en_US |
dc.description.version | publishedVersion | en_US |
dc.source.pagenumber | 1254-1267 | en_US |
dc.source.volume | 51 | en_US |
dc.source.journal | International Journal of Epidemiology | en_US |
dc.source.issue | 4 | en_US |
dc.identifier.doi | 10.1093/ije/dyab251 | |
dc.identifier.cristin | 2067391 | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |