Using Mendelian randomisation to assess causality in observational studies

Panagiota Pagoni, Niki Dimou, Neil Murphy, Evie Stergiakouli

Research output: Contribution to journalReview article (Academic Journal)peer-review

5 Citations (Scopus)
144 Downloads (Pure)

Abstract

Objective Mendelian randomisation (MR) is a technique that aims to assess causal effects of exposures on disease outcomes. The paper aims to present the main assumptions that underlie MR, the statistical methods used to estimate causal effects and how to account for potential violations of the key assumptions. Methods We discuss the key assumptions that should be satisfied in an MR setting. We list the statistical methodologies used in two-sample MR when summary data are available to estimate causal effects (ie, Wald ratio estimator, inverse-variance weighted and maximum likelihood method) and identify/adjust for potential violations of MR assumptions (ie, MR-Egger regression and weighted Median approach). We also present statistical methods and graphical tools used to evaluate the presence of heterogeneity. Results We use as an illustrative example of a published two-sample MR study, investigating the causal association of body mass index with three psychiatric disorders (ie, bipolar disorder, schizophrenia and major depressive disorder). We highlight the importance of assessing the results of all available methods rather than each method alone. We also demonstrate the impact of heterogeneity in the estimation of the causal effects. Conclusions MR is a useful tool to assess causality of risk factors in medical research. Assessment of the key assumptions underlying MR is crucial for a valid interpretation of the results.

Original languageEnglish
Pages (from-to)67-71
Number of pages5
JournalEvidence-Based Mental Health
Volume22
Issue number2
Early online date25 Apr 2019
DOIs
Publication statusPublished - 1 May 2019

Keywords

  • Schizophrenia and psychotic disorders

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