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

被引：17

作者：

Power, Grace M. ^{[1
,2
,3
]}

Sanderson, Eleanor ^{[1
,2
]}

Pagoni, Panagiota ^{[1
,2
]}

Fraser, Abigail ^{[1
,2
]}

Morris, Tim ^{[4
]}

Prince, Claire ^{[1
,2
]}

Frayling, Timothy M. ^{[5
]}

Heron, Jon ^{[1
,2
]}

Richardson, Tom G. ^{[1
,2
]}

Richmond, Rebecca ^{[1
,2
]}

Tyrrell, Jessica ^{[5
]}

Warrington, Nicole ^{[3
,6
]}

Davey Smith, George ^{[1
,2
,3
,7
]}

Howe, Laura D. ^{[1
,2
]}

Tilling, Kate M. ^{[1
,2
]}

机构：

[1] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, England

[2] Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Oakfield House,Oakfield Grove, Bristol BS8 2BN, England

[3] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[4] UCL, Social Res Inst, Ctr Longitudinal Studies, London, England

[5] Univ Exeter, Coll Med & Hlth, Genet Complex Traits, Exeter, Devon, England

[6] Univ Queensland, Frazer Inst, Woolloongabba, Qld, Australia

[7] Univ Bristol, Univ Hosp Bristol & Weston NHS Fdn Trust, NIHR Bristol Biomed Res Ctr BRC, Bristol, England

来源：

EUROPEAN JOURNAL OF EPIDEMIOLOGY | 2024年 / 39卷 / 05期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

Lifecourse; Mendelian randomisation; Systematic literature review; Methodology; PRENATAL ALCOHOL EXPOSURE; OFFSPRING BIRTH-WEIGHT; CORONARY HEART-DISEASE; TIME-VARYING EXPOSURE; BODY-MASS INDEX; DNA METHYLATION; MATERNAL HOMOCYSTEINE; ATRIAL-FIBRILLATION; CAUSAL RELATIONSHIP; AGE;

D O I：

10.1007/s10654-023-01032-1

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

1004 ; 120402 ;

摘要：

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.

引用

页码：501 / 520

页数：20