title: Further evidence for genetic variation at the serotonin transporter gene SLC6A4 contributing toward anxiety.
abstract: Social anxiety disorder (SAD) is a common and heritable psychiatric disorder. However, genetic studies in SAD are rare and only a few candidate genes have been implicated so far. In the present study, we investigated whether single-nucleotide polymorphisms (SNPs) associated with other psychiatric disorders also contribute toward the development of SAD and followed up variants associated with SAD on the phenotypic level.
  
  
  
  We genotyped a total of 24 SNPs in a German sample of 321 SAD patients and 804 controls. We carried out single-marker analyses as well as quantitative association analyses of SAD severity and harm avoidance.
  
  
  
  None of the variants investigated showed an association with SAD in our case-control sample after Bonferroni correction. Two SNPs reached nominal significance (rs818702, P=0.032; rs140701, P=0.048). Of these, only rs140701 showed an association in the same allelic direction as reported previously. This SNP is located within the serotonin transporter gene SLC6A4, which is the primary target of selective-serotonin reuptake inhibitors used for the treatment of depressive and anxiety disorders. The quantitative association analysis of all cases with available data on symptom severity showed four SNPs with a nominal significant association. Among these SNPs, rs10994359 showed the strongest association (P=0.001) and was located near the ANK3 gene. In addition, rs10994359 was nominally associated with harm avoidance scores (P=0.001).
  
  
  
  Our results provide further evidence for an involvement of the serotonin transporter gene SLC6A4 in the etiology of anxiety-related traits. Furthermore, our study implicates that genetic variation at the genome-wide associated bipolar disorder locus ANK3 might influence anxiety-related personality traits.
authors.affiliation: aInstitute of Human Genetics bDepartment of Genomics, Life and Brain Center cClinic for Psychosomatic Medicine and Psychotherapy, University of Bonn, Bonn dDepartment of Psychotherapy and Psychosomatic Medicine, University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Dresden, Germany eDepartment of Psychiatry (UPK) fHuman Genomics Research Group, Department of Biomedicine, University of Basel gInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Forstner
authors.forename: Stefanie
authors.initials: S
authors.lastname: Rambau
authors.forename: Nina
authors.initials: N
authors.lastname: Friedrich
authors.forename: Kerstin U
authors.initials: KU
authors.lastname: Ludwig
authors.forename: Anne C
authors.initials: AC
authors.lastname: Böhmer
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
authors.forename: Anna
authors.initials: A
authors.lastname: Maaser
authors.forename: Timo
authors.initials: T
authors.lastname: Hess
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kleiman
authors.forename: Antje
authors.initials: A
authors.lastname: Bittner
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Jessica
authors.initials: J
authors.lastname: Becker
authors.forename: Franziska
authors.initials: F
authors.lastname: Geiser
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
authors.forename: Rupert
authors.initials: R
authors.lastname: Conrad
mesh_terms: D000328:Adult; D001007:Anxiety / Q000235:genetics / Q000378:metabolism; D001008:Anxiety Disorders / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D005858:Germany; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins