The power of sample size and homogenous sampling: association between the 5-HTTLPR serotonin transporter polymorphism and major depressive disorder.
BACKGROUND
Several lines of evidence indicate that abnormalities in the functioning of the central serotonergic system are involved in the pathogenesis of affective illness. A 44-base-pair insertion/deletion polymorphism in the 5' regulatory region of the serotonin transporter gene (5-HTTLPR), which influences expression of the serotonin transporter, has been the focus of intensive research since an initial report on an association between 5-HTTLPR and depression-related personality traits. Consistently replicated evidence for an involvement of this polymorphism in the etiology of mood disorders, particularly in major depressive disorder (MDD), remains scant.


METHODS
We assessed a potential association between 5-HTTLPR and MDD, using the largest reported sample to date (466 patients, 836 control subjects). Individuals were all of German descent. Patients were systematically recruited from consecutive inpatient admissions. Control subjects were drawn from random lists of the local Census Bureau and screened for psychiatric disorders.


RESULTS
The short allele of 5-HTTLPR was significantly more frequent in patients than in control subjects (45.5% vs. 39.9%; p = .006; odds ratio = 1.26).


CONCLUSIONS
These results support an involvement of 5-HTTLPR in the etiology of MDD. They also demonstrate that the detection of small genetic effects requires very large and homogenous samples.
Hoefgen
Barbara
B
Department of Psychiatry, University of Bonn, Germany.
Schulze
Thomas G
TG
Ohlraun
Stephanie
S
von Widdern
Olrik
O
Höfels
Susanne
S
Gross
Magdalena
M
Heidmann
Vivien
V
Kovalenko
Svetlana
S
Eckermann
Anita
A
Kölsch
Heike
H
Metten
Martin
M
Zobel
Astrid
A
Becker
Tim
T
Nöthen
Markus M
MM
Propping
Peter
P
Heun
Reinhard
R
Maier
Wolfgang
W
Rietschel
Marcella
M
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins