Further evidence for genetic variation at the serotonin transporter gene SLC6A4 contributing toward anxiety

Psychiatr Genet. 2017 Jun;27(3):96-102. doi: 10.1097/YPG.0000000000000171.


Objectives: 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.

Patients and methods: 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.

Results: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anxiety / genetics
  • Anxiety / metabolism
  • Anxiety Disorders / genetics*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation
  • Genotype
  • Germany
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Serotonin Plasma Membrane Transport Proteins / metabolism


  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins