dc.contributor | University of Akureyri |
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 E. |
dc.contributor.author | Gilly, Arthur |
dc.contributor.author | Ingvarsson, Þorvaldur |
dc.contributor.author | Johnsen, Marianne B. |
dc.contributor.author | Jónsson, Helgi |
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 | Stefánsson, Kári |
dc.contributor.author | Uitterlinden, André G. |
dc.contributor.author | Winsvold, Bendik |
dc.contributor.author | Zwart, John Anker |
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 | 2023-06-09T01:03:42Z |
dc.date.available | 2023-06-09T01:03:42Z |
dc.date.issued | 2022-08-01 |
dc.identifier.citation | Hartley , A , Sanderson , E , Granell , R , Paternoster , L , Zheng , J , Smith , G D , Southam , L , Hatzikotoulas , K , Boer , C G , Van Meurs , J , Zeggini , E , Gregson , C L , Tobias , J H , Stefánsdóttir , L , Zhang , Y , De Almeida , R C , Wu , T T , Teder-Laving , M , Skogholt , A H , Terao , C , Zengini , E , Alexiadis , G , Barysenka , A , Bjornsdottir , G , Gabrielsen , M E , Gilly , A , Ingvarsson , Þ , Johnsen , M B , Jónsson , H , Kloppenburg , M G , Luetge , A , Mägi , R , Mangino , M , Nelissen , R R G H H , Shivakumar , M , Steinberg , J , Takuwa , H , Thomas , L , Tuerlings , M , Babis , G , Cheung , J P Y , Samartzis , D , Lietman , S A , Slagboom , P E , Stefánsson , K , Uitterlinden , A G , Winsvold , B , Zwart , J A , Sham , P C , Thorleifsson , G , Gaunt , T R , Morris , A P , Valdes , A M , Tsezou , A , Cheah , K S E , Ikegawa , S , Hveem , K , Esko , T , Wilkinson , J M , Meulenbelt , I , Michael Lee , M T & Styrkársdóttir , U 2022 , ' Using multivariable Mendelian randomization to estimate the causal effect of bone mineral density on osteoarthritis risk, independently of body mass index ' , International Journal of Epidemiology , vol. 51 , no. 4 , pp. 1254-1267 . https://doi.org/10.1093/ije/dyab251 |
dc.identifier.issn | 0300-5771 |
dc.identifier.other | 145374366 |
dc.identifier.other | 80522947-c73b-4a75-80a6-d12dbceedd28 |
dc.identifier.other | 85135580972 |
dc.identifier.other | 34897459 |
dc.identifier.uri | https://hdl.handle.net/20.500.11815/4234 |
dc.description | Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press on behalf of the International Epidemiological Association. |
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. |
dc.format.extent | 14 |
dc.format.extent | 805018 |
dc.format.extent | 1254-1267 |
dc.language.iso | en |
dc.relation.ispartofseries | International Journal of Epidemiology; 51(4) |
dc.rights | info:eu-repo/semantics/openAccess |
dc.subject | body mass index |
dc.subject | bone mineral density |
dc.subject | Mendelian randomization |
dc.subject | Osteoarthritis |
dc.subject | UK Biobank |
dc.subject | Epidemiology |
dc.title | Using multivariable Mendelian randomization to estimate the causal effect of bone mineral density on osteoarthritis risk, independently of body mass index |
dc.type | /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article |
dc.description.version | Peer reviewed |
dc.identifier.doi | 10.1093/ije/dyab251 |
dc.relation.url | http://www.scopus.com/inward/record.url?scp=85135580972&partnerID=8YFLogxK |
dc.contributor.department | Office of Division of Diagnostic and Support Services |
dc.contributor.department | Faculty of Medicine |
dc.contributor.department | Internal Medicine and Emergency Services |