Guidelines for performing Mendelian randomization investigations

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

doi:10.12688/wellcomeopenres.15555.2

Guidelines for performing Mendelian randomization investigations

Wellcome Open Res. 2020 Apr 28;4:186. doi: 10.12688/wellcomeopenres.15555.2. eCollection 2019.

Authors

Stephen Burgess^{1

2}, George Davey Smith^{3

4}, Neil M Davies^{3

4}, Frank Dudbridge⁵, Dipender Gill⁶, M Maria Glymour⁷, Fernando P Hartwig^{3

8}, Michael V Holmes^{9

10}, Cosetta Minelli¹¹, Caroline L Relton^{3

4}, Evropi Theodoratou^{12

13}

Affiliations

¹ MRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
² 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 Department of Health Sciences, University of Leicester, Leicester, UK.
⁶ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
⁷ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
⁸ Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
⁹ MRC Population Health Research Unit at the University of Oxford, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
¹⁰ Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
¹¹ National Heart and Lung Institute, Imperial College London, London, UK.
¹² Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK.
¹³ Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, 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 nine 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), 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 18 months.

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

Abstract

Grant support