Guidelines for performing Mendelian randomization investigations: update for summer 2023

Stephen Burgess; George Davey Smith; Neil M Davies; Frank Dudbridge; Dipender Gill; M Maria Glymour; Fernando P Hartwig; Zoltán Kutalik; Michael V Holmes; Cosetta Minelli; Jean V Morrison; Wei Pan; Caroline L Relton; Evropi Theodoratou

doi:10.12688/wellcomeopenres.15555.3

Guidelines for performing Mendelian randomization investigations: update for summer 2023

Wellcome Open Res. 2023 Aug 4:4:186. doi: 10.12688/wellcomeopenres.15555.3. eCollection 2019.

Authors

Stephen Burgess^{1

2}, George Davey Smith^{3

4}, Neil M Davies^{3

5

6

7}, Frank Dudbridge⁸, Dipender Gill⁹, M Maria Glymour¹⁰, Fernando P Hartwig^{3

11}, Zoltán Kutalik^{12

13

14}, Michael V Holmes^{15

16}, Cosetta Minelli¹⁷, Jean V Morrison¹⁸, Wei Pan¹⁹, Caroline L Relton^{3

4

20}, Evropi Theodoratou^{21

22}

Affiliations

¹ MRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
² BHF Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, UK.
³ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁴ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
⁵ Division of Psychiatry, University College London, London, UK.
⁶ Department of Statistical Sciences, University College London, London, WC1E 6BT, UK.
⁷ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
⁸ Department of Health Sciences, University of Leicester, Leicester, UK.
⁹ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
¹⁰ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
¹¹ Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
¹² Swiss Institute of Bioinformatics, Lausanne, Switzerland.
¹³ Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
¹⁴ University Center for Primary Care and Public Health (Unisanté), Lausanne, Switzerland.
¹⁵ MRC Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
¹⁶ Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
¹⁷ National Heart and Lung Institute, Imperial College London, London, UK.
¹⁸ Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
¹⁹ Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA.
²⁰ London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
²¹ Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK.
²² Edinburgh Cancer Research Centre, Institute of Genetics and Cancer, The University of Edinburgh, Edinburgh, UK.

Abstract

This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, and at journal editors and reviewers seeking to assess Mendelian randomization manuscripts. The guidelines are divided into ten sections: motivation and scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary and sensitivity analyses (one section on robust statistical methods and one on other approaches), extensions and additional analyses, data presentation, and interpretation. These guidelines will be updated based on feedback from the community and advances in the field. Updates will be made periodically as needed, and at least every 24 months.

Keywords: Mendelian randomization; causal inference; genetic epidemiology; guidelines.

Abstract

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