The serotonin transporter promoter repeat length polymorphism, seasonal affective disorder and seasonality.
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.


METHODS
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.
Johansson
C
C
Department of Molecular Medicine, Karolinska Institute and Karolinska Hospital, Stockholm, Sweden.
Willeit
M
M
Levitan
R
R
Partonen
T
T
Smedh
C
C
Del Favero
J
J
Bel Kacem
S
S
Praschak-Rieder
N
N
Neumeister
A
A
Masellis
M
M
Basile
V
V
Zill
P
P
Bondy
B
B
Paunio
T
T
Kasper
S
S
Van Broeckhoven
C
C
Nilsson
L G
LG
Lam
R
R
Schalling
M
M
Adolfsson
R
R
D000328:Adult; D000339:Affect; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016574:Seasonal Affective Disorder / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D012621:Seasons; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin