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To the Editor: In their meta-analysis, Dr Risch and colleagues¹ reported on gene-environment interactions in depressive disorders, focusing on the interaction between the serotonin transporter promoter polymorphism and life events. They stated that "the samples, study designs, measures, and analyses were highly divergent across studies, thereby limiting the comparability of the studies and their evidence regarding replication." However, the authors did not address 2 other problems arising from the methodology of their meta-analysis.

First, although some original studies used a nondichotomized dimensional outcome and thus reported additive interaction effects, the study by Risch and colleagues¹ applied a multiplicative or log-additive model to estimate the interaction effects for a dichotomized outcome in all studies. Thus, studies that previously reported significant gene-environment interaction effects with a dimensional outcome measure in an additive model, such as the study by Grabe et al,² lost this effect in a multiplicative model with an arbitrary dichotomization . . . [Full Text of this Article]

Christian Schwahn, PhD
schwahn@uni-greifswald.de
Institute of Epidemiology and Social Medicine

Hans Jörgen Grabe, MD
Department of Psychiatry and Psychotherapy
University of Greifswald
Greifswald, Germany

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