Background. Conflicting results have been reported in previous association studies of the serotonin transporter promoter repeat length polymorphism (5-HTTLPR), seasonal affective disorder (SAD) and seasonality (seasonal variations in mood and behaviour). The aim of this study was to test for association in new case–control and population-based materials, and to perform a combined analysis of all published studies of 5-HTTLPR and SAD.
Method. One hundred and forty-seven new SAD cases and 115 controls were genotyped for 5-HTTLPR and in total 464 patients and 414 controls were included in the pooled analysis. In addition, 226 individuals selected for unusually high or low seasonality scores from a population based material and 46 patients with non-seasonal depression were analysed. Different genetic models were tested and seasonality was analysed both as a qualitative (high v. low) and as a quantitative trait in the different sample sets.
Results. No association between 5-HTTLPR and SAD was found in the new case–control material, in the combined analysis of all samples, or when only including 316 patients with controls (N=298) selected for low seasonality. A difference was detected between the population based high and low seasonality groups, when assuming a recessive effect of the short allele (20% and 10% short allele homozygotes, respectively, OR (95% CI): 2·24 (1·03–4·91)). Quantitative analysis of seasonality revealed no association with 5-HTTLPR in any sample set.
Conclusions. These results do not suggest a major role of the short variant of 5-HTTLPR in susceptibility to SAD, but provide modest evidence for an effect on seasonality.
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