title: Genome-wide association data provide further support for an association between 5-HTTLPR and major depressive disorder.
abstract: BACKGROUND
  Dysfunctions of serotonergic neurotransmission are supposed to be involved in the pathogenesis of psychiatric disorders such as major depressive disorder (MDD). The concentration of serotonin (5-hydroxytryptamine, 5-HT) in the synaptic cleft is essentially regulated by the 5-HT transporter (5-HTT). A length polymorphism repeat in the 5-HTT promoter region, termed 5-HTTLPR, has been commonly investigated for an association with psychiatric disorders.
  
  
  METHODS
  Genotyping of the 5-HTTLPR is time-consuming and technically challenging. Recently, a two-SNP haplotype was identified that tags the 5-HTTLPR at r(2)=0.775. This allows extraction of 5-HTTLPR genotype information from large genome-wide association study (GWAS) data sets. In the present study we performed haplotype analysis using a German GWAS case-control dataset to test for an association between MDD and the two-SNP tagging haplotype for 5-HTTLPR.
  
  
  RESULTS
  We detected a significant association between the TA haplotype (tagging the S-allele of the 5-HTTLPR) and MDD. Our result is consistent with previous findings of an association between the 5-HTTLPR S-allele and MDD.
  
  
  CONCLUSIONS
  Using the two-SNP tagging haplotype did not allow testing of the tri-allelic genotype (but only the two-allelic genotype). This and the fact that the haplotype tags the 5-HTTLPR with an imperfect linkage disequilibrium of r(2)=0.775 may lead to some loss of power.
  
  
  CONCLUSIONS
  Our results provide further support for an involvement of the 5-HTTLPR in MDD and represent the first example of demonstrating association between MDD and the S-allele of the length polymorphism repeat using common SNP information from SNP-array data.
authors.affiliation: Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Haenisch
authors.forename: Stefan
authors.initials: S
authors.lastname: Herms
authors.forename: Manuel
authors.initials: M
authors.lastname: Mattheisen
authors.forename: Michael
authors.initials: M
authors.lastname: Steffens
authors.forename: Rene
authors.initials: R
authors.lastname: Breuer
authors.forename: Jana
authors.initials: J
authors.lastname: Strohmaier
authors.forename: Franziska
authors.initials: F
authors.lastname: Degenhardt
authors.forename: Christine
authors.initials: C
authors.lastname: Schmäl
authors.forename: Susanne
authors.initials: S
authors.lastname: Lucae
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins