Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: a systematic literature review

Power, Grace M., Sanderson, Eleanor, Pagoni, Panagiota ORCID: https://orcid.org/0000-0002-8090-512X, Fraser, Abigail, Morris, Tim, Prince, Claire, Frayling, Timothy M., Heron, Jon, Richardson, Tom G., Richmond, Rebecca, Tyrrell, Jessica, Warrington, Nicole, Davey Smith, George, Howe, Laura D. and Tilling, Kate M. 2024. Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: a systematic literature review. European Journal of Epidemiology 39 (5) , pp. 501-520. 10.1007/s10654-023-01032-1

Full text not available from this repository.

Abstract

Diseases diagnosed in adulthood may have antecedents throughout (including prenatal) life. Gaining a better understanding of how exposures at different stages in the lifecourse influence health outcomes is key to elucidating the potential benefits of disease prevention strategies. Mendelian randomisation (MR) is increasingly used to estimate causal effects of exposures across the lifecourse on later life outcomes. This systematic literature review explores MR methods used to perform lifecourse investigations and reviews previous work that has utilised MR to elucidate the effects of factors acting at different stages of the lifecourse. We conducted searches in PubMed, Embase, Medline and MedRXiv databases. Thirteen methodological studies were identified. Four studies focused on the impact of time-varying exposures in the interpretation of “standard” MR techniques, five presented methods for repeat measures of the same exposure, and four described methodological approaches to handling multigenerational exposures. A further 127 studies presented the results of an applied research question. Over half of these estimated effects in a single generation and were largely confined to the exploration of questions regarding body composition. The remaining mostly estimated maternal effects. There is a growing body of research focused on the development and application of MR methods to address lifecourse research questions. The underlying assumptions require careful consideration and the interpretation of results rely on select conditions. Whilst we do not advocate for a particular strategy, we encourage practitioners to make informed decisions on how to approach a research question in this field with a solid understanding of the limitations present and how these may be affected by the research question, modelling approach, instrument selection, and data availability.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Springer
ISSN:	0393-2990
Date of Acceptance:	21 July 2023
Last Modified:	09 Aug 2024 11:00
URI:	https://orca.cardiff.ac.uk/id/eprint/171150

Actions (repository staff only)

Edit Item