ISSN 2051-8315
Psychopathology Review
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 Volume 4, Issue 1, 4-25, 2015
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Causal inference in psychopathology: A systematic review of Mendelian randomisation studies aiming to identify environmental risk factors for psychopathology

  Jean-Baptiste Pingault - University College London, UK
  Charlotte Cecil - University College London, UK
  Joseph Murray - University of Cambridge, UK
  Marcus Munafo - University of Bristol, UK
  Essi Viding - University College London, UK

Volume 4, Issue 1, 2015, Pages 4-25

Psychopathology represents a leading cause of disability worldwide. Effective interventions need to target risk factors that are causally related to psychopathology. In order to distinguish between causal and spurious risk factors, it is critical to account for, environmental and genetic confounding. Mendelian randomisation studies use genetic variants that are independent from environmental and genetic confounders in order to strengthen causal inference. We conducted a systematic review of fifteen studies using Mendelian randomisation to examine the causal role of putative risk factors for psychopathology related outcomes including depression, anxiety, psychological distress, schizophrenia, substance abuse/antisocial behaviour, and smoking initiation. The most commonly examined risk factors in the reviewed Mendelian randomisation studies were smoking, alcohol use and body mass index. In most cases, risk factors were strongly associated with psychopathology-related outcomes in conventional analyses. Conversely, Mendelian randomisation analyses provided very little consistent evidence that any of these associations were causal. We discuss possible reasons for these diverging results between conventional and Mendelian randomisation analyses and outline future directions for progressing research in ways that maximises the potential for identifying targets for intervention.

Table of Contents
Causal inference in psychopathology
Modifiable environmental exposures and genetic instruments
Principles of Mendelian randomisation
Limitations of Mendelian randomisation
 Inclusion criteria
 Search strategy
 Study selection
 Reasons for null and contradictory findings
 Future directions: Increasing the scope of MR studies

Correspondence to
Dr Jean-Baptiste Pingault

Genetically-informative desgins, causal inference, Mendelian randomisation, psychopathology, risk factors

Received 6 Apr 2015; Revised 21 Sep 2015; Accepted 21 Sep 2015; In Press 21 Feb 2016

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