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Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: A systematic literature review
European Journal of Epidemiology ( IF 13.6 ) Pub Date : 2023-11-08 , DOI: 10.1007/s10654-023-01032-1
Grace M Power 1, 2, 3 , Eleanor Sanderson 1, 2 , Panagiota Pagoni 1, 2 , Abigail Fraser 1, 2 , Tim Morris 4 , Claire Prince 1, 2 , Timothy M Frayling 5 , Jon Heron 1, 2 , Tom G Richardson 1, 2 , Rebecca Richmond 1, 2 , Jessica Tyrrell 5 , Nicole Warrington 3, 6 , George Davey Smith 1, 2, 3, 7 , Laura D Howe 1, 2 , Kate M Tilling 1, 2
Affiliation  

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.



中文翻译:

孟德尔随机化在生命历程流行病学中应用的方法论方法、挑战和机遇:系统文献综述

成年期诊断出的疾病可能有贯穿一生(包括产前)的前因。更好地了解生命周期不同阶段的暴露如何影响健康结果是阐明疾病预防策略的潜在益处的关键。孟德尔随机化 (MR) 越来越多地用于估计整个生命过程中的暴露对以后生活结果的因果影响。这篇系统文献综述探讨了用于进行生命历程调查的 MR 方法,并回顾了以前利用 MR 来阐明生命历程不同阶段因素影响的工作。我们在 PubMed、Embase、Medline 和 MedRXiv 数据库中进行了检索。确定了十三项方法学研究。四项研究重点关注时变暴露对“标准”MR 技术解释的影响,五项研究提出了重复测量相同暴露的方法,四项研究描述了处理多代暴露的方法。另外 127 项研究提出了应用研究问题的结果。超过一半的估计影响是在一代人的时间内产生的,并且主要局限于对身体成分问题的探索。其余的大部分是估计母体影响。越来越多的研究集中在 MR 方法的开发和应用上,以解决生命历程研究问题。基本假设需要仔细考虑,结果的解释依赖于选定的条件。虽然我们不提倡特定的策略,但我们鼓励从业者就如何处理该领域的研究问题做出明智的决定,并充分了解目前的局限性以及这些局限性如何受到研究问题、建模方法、工具的影响。选择和数据可用性。

更新日期:2023-11-09
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