A guide for understanding and designing Mendelian randomization studies in the musculoskeletal field

Research output: Contribution to journalReview article (Academic Journal)peer-review

9 Citations (Scopus)
150 Downloads (Pure)

Abstract

Mendelian randomization (MR) is an increasingly popular component of an epidemiologist's toolkit, used to provide evidence of a causal effect of one trait (an exposure, eg, body mass index [BMI]) on an outcome trait or disease (eg, osteoarthritis). Identifying these effects is important for understanding disease etiology and potentially identifying targets for therapeutic intervention. MR uses genetic variants as instrumental variables for the exposure, which should not be influenced by the outcome or confounding variables, overcoming key limitations of traditional epidemiological analyses. For MR to generate a valid estimate of effect, key assumptions must be met. In recent years, there has been a rapid rise in MR methods that aim to test, or are robust to violations of, these assumptions. In this review, we provide an overview of MR for a non-expert audience, including an explanation of these key assumptions and how they are often tested, to aid a better reading and understanding of the MR literature. We highlight some of these new methods and how they can be useful for specific methodological challenges in the musculoskeletal field, including for conditions or traits that share underlying biological pathways, such as bone and joint disease. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Original languageEnglish
Article numbere10675
JournalJBMR PLUS
Volume6
Issue number10
Early online date20 Aug 2022
DOIs
Publication statusPublished - 1 Oct 2022

Bibliographical note

Funding Information:
Supported by the National Key Research and Development Program of China (No. 2018YFC0309800), the National Natural Science Foundation of China (Nos. 42176021, 91858203), the Open Project Program of State Key Laboratory of Tropical Oceanography (No. LTOZZ2001), and the Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (No. GML2019ZD0304) 8 Acknowledgment

Funding Information:
All authors work in a unit funded by the Medical Research Council (MRC) and the University of Bristol (MC_UU_00011/1, MC_UU_00011/3). GMP is supported by the GW4 Biomed Doctoral Training Programme, awarded to the Universities of Bath, Bristol, Cardiff, and Exeter from the Medical Research Council (MRC)/UKRI (MR/N0137941/1). No individual-level data were analyzed for this review, and therefore ethics approval was not required for this study. Authors’ roles: conceptualization: AEH and GDS. Writing—original draft: AEH. Writing—review and editing: all authors.

Publisher Copyright:
© 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Fingerprint

Dive into the research topics of 'A guide for understanding and designing Mendelian randomization studies in the musculoskeletal field'. Together they form a unique fingerprint.

Cite this