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Mendelian randomization in the bone field.

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cam.issuedOnline2018-10-12
dc.contributor.authorLarsson, Susanna C
dc.contributor.authorMichaëlsson, Karl
dc.contributor.authorBurgess, Stephen
dc.contributor.orcidBurgess, Stephen [0000-0001-5365-8760]
dc.date.accessioned2018-11-23T00:33:33Z
dc.date.available2018-11-23T00:33:33Z
dc.date.issued2019-09
dc.description.abstractIdentification of causative risk factors amenable for modification is essential for the prevention and treatment of osteoporosis. Observational studies have identified associations between several potentially modifiable risk factors and osteoporosis. However, observational studies are susceptible to confounding, reverse causation bias, and measurement error, all of which limit their ability to provide causal estimates of the effect of exposures on outcomes, thereby reducing their ability to inform prevention and treatment strategies against bone loss and fractures. In addition, not all risk factors are suitable for an analysis in a randomized clinical trial. Mendelian randomization is a genetic epidemiological method that exploits genetic variants as unbiased proxies for modifiable exposures (e.g., biomarkers, adiposity measures, dietary factors, and behaviors) to determine the causal relationships between exposures and health outcomes. This technique has been used to provide evidence of causal associations of serum estradiol concentrations, smoking, body mass index, and type 2 diabetes with bone mineral density and the lack of associations of serum thyroid stimulating hormone, urate, C-reactive protein, and 25‑hydroxyvitamin D concentrations with bone mineral density in generally healthy populations. This review will briefly explain the concept of Mendelian randomization, the advantages and potential limitations of this study design, and give examples of how Mendelian randomization has been used to investigate questions relevant to osteoporosis.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.33208
dc.identifier.eissn1873-2763
dc.identifier.issn8756-3282
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285864
dc.languageeng
dc.language.isoeng
dc.publisherElsevier BV
dc.publisher.urlhttp://dx.doi.org/10.1016/j.bone.2018.10.011
dc.subjectBone mineral density
dc.subjectFracture
dc.subjectGenome-wide association studies
dc.subjectMendelian randomization
dc.subjectOsteoporosis
dc.subjectSingle nucleotide polymorphisms
dc.subjectAnimals
dc.subjectBody Mass Index
dc.subjectBone Density
dc.subjectBone and Bones
dc.subjectHumans
dc.subjectMendelian Randomization Analysis
dc.titleMendelian randomization in the bone field.
dc.typeArticle
dcterms.dateAccepted2018-10-11
prism.endingPage58
prism.publicationDate2019
prism.publicationNameBone
prism.startingPage51
prism.volume126
pubs.funder-project-idWellcome Trust (204623/Z/16/Z)
pubs.funder-project-idMedical Research Council (MR/L003120/1)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idMedical Research Council (MC_UU_00002/7)
rioxxterms.licenseref.startdate2019-09
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1016/j.bone.2018.10.011

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