The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Robust methods in Mendelian randomization via penalization of heterogeneous causal estimates
Open accessAbstract
Methods have been developed for Mendelian randomization that can obtain consistent causal estimates under weaker assumptions than the standard instrumental variable assumptions. The median-based estimator and MR-Egger are examples of such methods. However, these methods can be sensitive to genetic variants with heterogeneous causal estimates. Such heterogeneity may arise from over-dispersion in the causal estimates, or specific variants with outlying causal estimates. In this paper, we develop three extensions to robust methods for Mendelian randomization with summarized data: 1) robust regression (MM-estimation); 2) penalized weights; and 3) Lasso penalization. Methods using these approaches are considered in two applied examples: one where there is evidence of over-dispersion in the causal estimates (the causal effect of body mass index on schizophrenia risk), and the other containing outliers (the causal effect of low-density lipoprotein cholesterol on Alzheimer's disease risk). Through an extensive simulation study, we demonstrate that robust regression applied to the inverse-variance weighted method with penalized weights is a worthwhile additional sensitivity analysis for Mendelian randomization to provide robustness to variants with outlying causal estimates. The results from the applied examples and simulation study highlight the importance of using methods that make different assumptions to assess the robustness of findings from Mendelian randomization investigations with multiple genetic variants.
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Citations
Cites
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“[25] for individual level data and adapt this method to be used with summary level data.”
Method
Cited by
Sanderson, E., Glymour, M. M., Holmes, M. V., Kang, H., Morrison, J., Munafò, M. R., Palmer, T., Schooling, C. M., Wallace, C., Zhao, Q., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00092-5 · Cited by 2,229
Guidelines for performing Mendelian randomization investigations
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Self-citationBjörnson, E., Adiels, M., Taskinen, M.-R., Burgess, S., Rawshani, A., Borén, J., & Packard, C. J. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad337 · Cited by 183
Self-citation
Metadata
- Authors
- Rees, J. M. B., Wood, A. M., Dudbridge, F., & Burgess, S.
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2019-09-23
- Volume
- 14
- Issue
- 9
- Pages
- e0222362
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2977182596
- Cited by
- 183
- References
- 19
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- gold
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