GL.05 Controversies in gene–environment interaction research: why all the fuss?
- M Munafò
Marcus Munafò was an undergraduate at the University of Oxford, before moving to the University of Southampton to complete an MSc in Health Psychology and a PhD. Following this, he returned to the University of Oxford, as a postdoctoral fellow in the Department of Public Health and Primary Care and later the Department of Clinical Pharmacology. In 2004–2005 he spent 6 months as a Visiting Professor at the University of Pennsylvania. In March 2005 took up a tenured position in the School of Experimental Psychology at the University of Bristol, where he is now Professor of Biological Psychology and leads the Tobacco and Alcohol Research Group, and the Psychopharmacology Research Network.
His research interests are in the integration of multiple research perspectives to understand individual differences in smoking behaviour and, in particular, smoking cessation. This has included substantial work on smoking cessation pharmacogenetics, including analysis of the likely cost-effectiveness of personalised medicine. His research also includes the study of behavioural and neuroimaging correlates of smoking behaviour. He recently contributed material on the genetics of smoking behaviour and smoking cessation pharmacogenetics to the forthcoming Surgeon General's Report on tobacco-related disease.
In 2004 he was awarded the Society for Research on Nicotine and Tobacco Young Investigator Award, and in 2005 the European College of Neuropsychopharmacology Fellowship Award. He is Past-President of the Society for Research on Nicotine and Tobacco Europe, and serves on the editorial board of several journals, including as Deputy Editor for Nicotine and Tobacco Research, and Senior Editor for Addiction. He serves on the addiction Scientific Advisory Panel for the European College of Neuropsychopharmacology, and has provided consultancy for the European Commission on two working groups, on smokeless tobacco products and tobacco additives. He has also advised the Commission on Human Medicines in the UK.
There has been considerable interest in recent years in the role of gene×environment (G×E) interactions in the aetiology of psychiatric disorders. While the fact that genetic effects may moderate the effects of environmental exposure is widely accepted, and supported by family and twin studies, there is controversy regarding the degree of evidence for specific G×E interactions reported in the literature. Here the various reasons for this ongoing controversy, and the extent to which this debate has polarised the field of G×E research, are discussed.
A number of relevant factors influencing the weight of evidence for specific G×E interactions will be discussed, including the degree of stringency employed in the definition of “replication”, the impact of different statistical models used to test for these interactions, and the statistical power of individual studies. In only a minority of studies is a replication reported that is qualitatively comparable to that in the original report, which may or may not mean that the original finding was spurious. Given reasonable assumptions regarding likely genetic and environmental effects, simulations indicate that many published studies may be underpowered, suggesting that some positive results for widely reported G×E interactions may indeed be compatible with chance findings.
Many difficulties arise from the use of existing datasets, which obscures whether different findings across studies are due to characteristics of the data (eg, questionnaire vs interview measures, sample characteristics), genuine effect heterogeneity, or simply chance. A further difficulty is the temptation to mine datasets for nominally significant results, which raises the risk of spurious findings (further exacerbated when interaction effects in the absence of main effects are observed). Recommendations for future studies will be discussed.