The power of sample size and homogenous sampling: Association between the 5-HTTLPR serotonin transporter polymorphism and major depressive disorder

• Published in: Biological psychiatry (1969) 2005-02, Vol.57 (3), p.247-251
• Main Authors: Hoefgen, Barbara, Schulze, Thomas G., Ohlraun, Stephanie, von Widdern, Olrik, Höfels, Susanne, Gross, Magdalena, Heidmann, Vivien, Kovalenko, Svetlana, Eckermann, Anita, Kölsch, Heike, Metten, Martin, Zobel, Astrid, Becker, Tim, Nöthen, Markus M., Propping, Peter, Heun, Reinhard, Maier, Wolfgang, Rietschel, Marcella
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Affective disorder; Aged; Behavioral psychophysiology; Biological and medical sciences; Case-Control Studies; Depression; Depressive Disorder, Major - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genotype; Humans; Linkage Disequilibrium; Male; Medical sciences; Membrane Glycoproteins - genetics; Membrane Transport Proteins - genetics; Middle Aged; Mood disorders; Nerve Tissue Proteins - genetics; Neurotransmission and behavior; neurotransmitter; Phenotype; Polymorphism, Genetic; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Serotonin Plasma Membrane Transport Proteins; stressful life events; suicide
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2004.11.027

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. 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. 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). 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.