TY - JOUR
T1 - Lack of Evidence for Association of the Serotonin Transporter Gene SLC6A4 with Autism
AU - Ramoz, Nicolas
AU - Reichert, Jennifer G.
AU - Corwin, Thomas E.
AU - Smith, Christopher J.
AU - Silverman, Jeremy M.
AU - Hollander, Eric
AU - Buxbaum, Joseph D.
N1 - Funding Information:
This work was supported by the Seaver Autism Research Center and by the National Institutes of Health through a Studies to Advance Autism Research and Treatment grant (Grant No. MH-066673) and Grant No. NS-042165.
Funding Information:
We gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium and the participating AGRE families. The Autism Genetic Resource Exchange is a program of Cure Autism Now and is supported, in part, by grant MH64547 from the National Institute of Mental Health to Daniel H. Geschwind (PI).
PY - 2006/7/15
Y1 - 2006/7/15
N2 - Background: The serotonin transporter (5-HTT) has long been considered likely to play a role in autism. Hyperserotonemia has been consistently found in a proportion of autistic patients, and the use of selective serotonin reuptake inhibitors (SSRIs) can have a positive effect in treating some symptoms of autism. Specific variants of the 5-HTT gene, SLC6A4, especially the insertion-deletion 5-HTTLPR promoter locus, have been found to modulate its expression and transporter function. Methods: We examined the transmission of the short or long allele of 5-HTTLPR locus to affected individuals, using a large cohort of 352 families. In addition, we screened five single nucleotide polymorphisms (SNPs) in the 5′ region of SLC6A4 previously reported to be positively associated with autism, as well as 4 additional SNPs also in the 5′ region. Results: No association of the 5-HTTLPR locus with autism was found. Furthermore, no evidence for association of any of the nine SNPs covering the SLC6A4 gene, or any of their haplotypes, was observed in our study. Using obsessive-compulsive behaviors (OCB), severe OCBs or rigid-compulsive subsets of our cohort gave the same negative results. Conclusions: SLC6A4 variants do not appear to be significantly involved in the liability to autism.
AB - Background: The serotonin transporter (5-HTT) has long been considered likely to play a role in autism. Hyperserotonemia has been consistently found in a proportion of autistic patients, and the use of selective serotonin reuptake inhibitors (SSRIs) can have a positive effect in treating some symptoms of autism. Specific variants of the 5-HTT gene, SLC6A4, especially the insertion-deletion 5-HTTLPR promoter locus, have been found to modulate its expression and transporter function. Methods: We examined the transmission of the short or long allele of 5-HTTLPR locus to affected individuals, using a large cohort of 352 families. In addition, we screened five single nucleotide polymorphisms (SNPs) in the 5′ region of SLC6A4 previously reported to be positively associated with autism, as well as 4 additional SNPs also in the 5′ region. Results: No association of the 5-HTTLPR locus with autism was found. Furthermore, no evidence for association of any of the nine SNPs covering the SLC6A4 gene, or any of their haplotypes, was observed in our study. Using obsessive-compulsive behaviors (OCB), severe OCBs or rigid-compulsive subsets of our cohort gave the same negative results. Conclusions: SLC6A4 variants do not appear to be significantly involved in the liability to autism.
KW - 5-HTT
KW - 5-HTTLPR
KW - Autistic disorder
KW - haplotype
KW - obsessive-compulsive behaviors
KW - transmission disequilibrium test
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U2 - 10.1016/j.biopsych.2006.01.009
DO - 10.1016/j.biopsych.2006.01.009
M3 - Article
C2 - 16616719
AN - SCOPUS:33745712342
SN - 0006-3223
VL - 60
SP - 186
EP - 191
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 2
ER -