Reply

Abstract

Goldman et al. ( 1 Goldman D. Malhotra A.K. Goldberg T.E. Weinberger D.R. The role of COMT Val158Met in cognition. Biol Psychiatry. 2008; Google Scholar ) criticize the conclusions of our recent systematic and quantitative review of the literature pertaining to the putative association between the catechol-o-methyltransferase (COMT) Val158Met polymorphism and measures of cognitive function ( 2 Barnett J.H. Scoriels L. Munafo M.R. Meta-analysis of the cognitive effects of the catechol-O-methyltransferase gene Val158/108Met polymorphism. Biol Psychiatry. 2008; 64: 137-144 Abstract Full Text Full Text PDF PubMed Scopus (309) Google Scholar ). This is timely—meta-analysis is an increasingly popular tool for establishing the strength of evidence (or otherwise) of genetic associations and their likely magnitude ( 3 Munafo M.R. Flint J. Meta-analysis of genetic association studies. Trends Genet. 2004; 20: 439-444 Abstract Full Text Full Text PDF PubMed Scopus (544) Google Scholar ), but as with any methodology it has its limitations. It has also served to identify several potential reasons why early putative genetic associations fail to subsequently replicate, such as exaggerated early results, publication bias, and time lag bias ( 4 Ioannidis J.P. Ntzani E.E. Trikalinos T.A. Contopoulos-Ioannidis D.G. Replication validity of genetic association studies. Nat Genet. 2001; 29: 306-309 Crossref PubMed Scopus (1616) Google Scholar , 5 Ioannidis J.P. Trikalinos T.A. Ntzani E.E. Contopoulos-Ioannidis D.G. Genetic associations in large versus small studies: an empirical assessment. Lancet. 2003; 361: 567-571 Abstract Full Text Full Text PDF PubMed Scopus (503) Google Scholar ) as well as inflation of effect size estimates related to research location and Impact Factor of the journal in which the study is published ( 6 Munafo M.R. Attwood A.S. Flint J. Letter to the Editor: Bias in genetic association studies: effects of research location and resources. Psychol Med. 2008; 38: 1213-1214 Crossref PubMed Scopus (27) Google Scholar , 7 Munafo MR, Stothart G, Flint J (in press): Bias in genetic association studies and impact factor. Mol Psychiatry. Google Scholar ). The Role of COMT Val158Met in CognitionBiological PsychiatryVol. 65Issue 1PreviewDoes the meta-analysis of Barnett et al. (1), “Meta-Analysis of the Cognitive Effects of the Catechol-O-Methyltransferase Gene Val158/108Met Polymorphism,” justify their conclusion that “Despite initial promising results, the COMT Val158/108Met polymorphism appears to have little if any association with cognitive function”? We submit that this statement illustrates the potential shortcomings of a purely statistical evaluation of a domain of inquiry that has penetrated to the deeper level of biological mechanisms. Full-Text PDF