Autism and serotonin transporter gene polymorphisms: a systematic review and meta-analysis

Am J Med Genet B Neuropsychiatr Genet. 2008 Sep 5;147B(6):903-13. doi: 10.1002/ajmg.b.30720.


The serotonin transporter gene (5-HTT) plays a crucial role in serotonergic neurotransmission and has been found to be associated, with varying degrees of significance, with many diseases, including autism. Prior association studies of autism have yielded conflicting results regarding the association between two common 5-HTT polymorphisms, the promoter insertion/deletion (5-HTTLPR) and the intron 2 VNTR (STin2 VNTR). We conducted a systematic review and meta-analysis to test the following hypotheses: (i) there is an association between autism and either or both of the 5-HTTLPR and STin2 VNTR polymorphisms, and (ii) the S allele of 5-HTTLPR and/or the STin2.12 allele of the VNTR are the specific risk alleles for autism. All published family-based and population based studies were examined to determine the overall strength of association between 5-HTT polymorphisms and autism. After exclusion of studies with overlapping samples and studies whose data did not allow for calculation of an odds ratio, 16 studies were included for final analyses, all but two of which used a family-based design. The meta-analysis failed to find a significant overall association between either of the 5-HTT polymorphisms examined and autism. Further, no allelic transmission distortion was found when studies of simplex (11 studies) and multiplex (3 studies) family samples were analyzed separately. However, there was significant heterogeneity by ethnicity; family based studies of US mixed population samples showed preferential transmission of the S allele of 5-HTTLPR (S allele:L allele = 247:183), while there was no allelic distortion among the family-based studies of European and Asian samples.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Autistic Disorder / genetics*
  • DNA Mutational Analysis / methods
  • Gene Frequency
  • Haplotypes
  • Humans
  • Polymorphism, Genetic*
  • Serotonin Plasma Membrane Transport Proteins / genetics*


  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins