Power, Grace M;
Sanderson, Eleanor;
Pagoni, Panagiota;
Fraser, Abigail;
Morris, Tim;
Prince, Claire;
Frayling, Timothy M;
... Tilling, Kate M; + view all
(2023)
Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: A systematic literature review.
European Journal of Epidemiology
10.1007/s10654-023-01032-1.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: A systematic literature review |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s10654-023-01032-1 |
| Publisher version: | https://doi.org/10.1007/s10654-023-01032-1 |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Lifecourse, Mendelian randomisation, Methodology, Systematic literature review |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Education UCL > Provost and Vice Provost Offices > School of Education > UCL Institute of Education UCL > Provost and Vice Provost Offices > School of Education > UCL Institute of Education > IOE - Social Research Institute UCL > Provost and Vice Provost Offices > School of Education > UCL Institute of Education > IOE - Social Research Institute > IOE - Centre for Longitudinal Studies |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10181451 |
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