title: Meta-analysis of the association between two polymorphisms in the serotonin transporter gene and affective disorders.
abstract: Family, twin, and adoption studies show that psychiatric diseases including bipolar disorder (BP) and unipolar disorder (UP) have a substantial genetic component. For these illnesses, both positive and negative associations have been reported for two polymorphisms located in the serotonin transporter gene (5-HTT) on chromosome 17: a 17-base-pair (bp) variable-number tandem-repeat (VNTR) in intron 2 and a 44-bp insertion/deletion in the promoter region. Thus, associations between these 5-HTT polymorphisms and affective disorders remain unclear. The present work investigates these potential associations in meta-analyzes that maximize the power to find associations between each disease and the two 5-HTT polymorphisms. We applied meta-analysis techniques to case-control studies of two 5-HTT polymorphisms and two affective disorders (BP and UP), resulting in four meta-analyzes. For each polymorphism, we assessed the evidence for allelic associations, heterogeneity among studies, the influence of individual studies, and the potential for publication bias. The short allele(s) of the 44-bp insertion/deletion polymorphism showed a significant association for BP (odds ratio (OR) = 1.13, P = 0.001) but not UP. For the 17-bp VNTR, an increase in the number of tandem repeats had no significant association with any of the disorders. The small but significant effects of the 44-bp insertion/deletion polymorphism for BP is consistent with being one of many genes that contributes to the multi-factorial nature of these psychiatric disorders.
authors.affiliation: Department of Psychiatry, Harvard Medical School at the Massachusetts Mental Health Center, Boston, Massachusetts, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Lasky-Su
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Glatt
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
mesh_terms: D000483:Alleles; D005787:Gene Frequency; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D018598:Minisatellite Repeats / Q000235:genetics; D019964:Mood Disorders / Q000235:genetics*; D016254:Mutagenesis, Insertional / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017384:Sequence Deletion / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins
chemical_list: D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins