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Serotonin transporter gene and autism: a haplotype analysis in an Irish autistic population

Molecular Psychiatry volume 9, pages 587–593 (2004)Cite this article

Abstract

The role of the serotonin transporter (5-HTT) in the development of neuropsychiatric disorders has been widely investigated. Two polymorphisms, an insertion/deletion in the promoter region and a 12 repeat allele in a variable nucleotide tandem repeat (VNTR) in intron 2, drive higher expression of the 5-HTT gene. Four studies have shown nominally significant excess transmission of alleles of the 5-HTT gene in autism, while three studies have reported no excess transmission. This present study investigates the role of 5-HTT in the genetically homogenous Irish population. In all, 84 families were genotyped for five polymorphisms (three SNPs, a VNTR and an in/del). The analysis of allele transmissions using the transmission disequilibrium test (TDT) was undertaken and indicated preferential transmission of the short promoter allele (TDT P-value=0.0334). Linkage disequilibrium between markers was calculated and haplotypes were assessed for excess transmission and odds ratios (ORs) to affected children. A number of haplotypes, especially those involving and surrounding SNP10, showed evidence of association. The ORs ranged from 1.2 to 2.4. The most significant haplotype associated with transmission to affected probands was the SNP10–VNTR–SNP18 haplotype (χ2=7.3023, P=0.0069, odds ratio=1.8). This haplotype included the 12 repeat allele of the VNTR, which is associated with increased expression and may play a subtle role in the early development of the brain in affected probands.

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Acknowledgements

We thank all the families who participated in this study. This study was supported by funding from the Health Research Board, The Wellcome Trust and the National Alliance for Autism Research.

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Authors and Affiliations

  1. Department of Genetics, Smurfit Institute, Trinity College, Dublin, Ireland

    J Conroy, M Gill & L Gallagher

  2. Department of Psychiatry, Trinity College, Dublin, Ireland

    E Meally, G Kearney, M Fitzgerald, M Gill & L Gallagher

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  1. J Conroy
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Correspondence to J Conroy.

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Conroy, J., Meally, E., Kearney, G. et al. Serotonin transporter gene and autism: a haplotype analysis in an Irish autistic population. Mol Psychiatry 9, 587–593 (2004). https://doi.org/10.1038/sj.mp.4001459

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