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Assessment of the genetic and clinical determinants of hip fracture risk: Genome-wide association and Mendelian randomization study
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2022 (English)In: Cell Reports Medicine, E-ISSN 2666-3791 , Vol. 3, no 10, article id 100776Article in journal (Refereed) Published
Abstract [en]

Hip fracture is the clinically most important fracture, but the genetic architecture of hip fracture is unclear. Here, we perform a large-scale hip fracture genome-wide association study meta-analysis and Mendelian randomization study using five cohorts from European biobanks. The results show that five genetic signals associate with hip fractures. Among these, one signal associates with falls, but not with bone mineral density (BMD), while four signals are in loci known to be involved in bone biology. Mendelian randomization analyses demonstrate a strong causal effect of decreased femoral neck BMD and moderate causal effects of Alzheimer's disease and having ever smoked regularly on risk of hip fractures. The substantial causal effect of decreased femoral neck BMD on hip fractures in both young and old subjects and in both men and women supports the use of change in femoral neck BMD as a surrogate outcome for hip fractures in clinical trials.

Place, publisher, year, edition, pages
Elsevier, 2022. Vol. 3, no 10, article id 100776
Keywords [en]
bone mineral density, genome-wide association study, hip fracture, mendelian randomization
National Category
Orthopaedics
Identifiers
URN: urn:nbn:se:umu:diva-200666DOI: 10.1016/j.xcrm.2022.100776ISI: 000917310900008PubMedID: 36260985Scopus ID: 2-s2.0-85140071308OAI: oai:DiVA.org:umu-200666DiVA, id: diva2:1709066
Funder
Torsten Söderbergs stiftelseSwedish National Centre for Research in Sports, 87/06Wellcome trustKnut and Alice Wallenberg FoundationThe Lars Erik Lundberg Foundation for Research and EducationSwedish Research Council, K20006-72X-20155013The Kempe Foundations, JCK-1021EU, Horizon 2020, 810645Swedish Society of MedicineNovo NordiskUmeå University, ALFVLL:968:22-2005Umeå University, ALFVLL: 937-2006Umeå University, ALFVLL:223:11-2007Umeå University, ALFVLL:78151-2009Region Västerbotten, VLL:159:33-2007Available from: 2022-11-07 Created: 2022-11-07 Last updated: 2023-09-05Bibliographically approved

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Wibom, CarlPettersson-Kymmer, Ulrika

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CiteExportLink to record
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Citation style
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