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Identification of tag haplotypes for 5HTTLPR for different genome-wide SNP platforms

Molecular Psychiatry volume 16, pages 1073–1075 (2011)Cite this article

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The length polymorphism repeat (5HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4, also known as 5HTT) is extensively studied in the context of psychiatric phenotypes, particularly in major depressive disorder. However, investigation of this polymorphism in the context of the current generation of large-scale genome-wide association studies is precluded, as the genotyping technology is limited to single-nucleotide polymorphisms (SNPs). Using genome-wide and 5HTTLPR genotype data from a total of 2823 unrelated individuals, we show that no single SNP is in high linkage disequilibrium (LD) with 5HTTLPR but some two-SNP haplotypes provide reasonable predictors. Hence, two-SNP haplotypes can be used as proxies for 5HTTLPR in genome-wide association studies. Analyses are repeated for sets of SNPs that are included in different genome-wide SNP platforms.

The 5HTTLPR is defined by a length variation of a repetitive sequence with a short (484 base pairs, 14 repeat units) and a long allele (528 base pairs, 16 repeat units) on chromosome 17. The basal activity of the long allele transcript is about threefold higher than that of the short allele, resulting in induced expression and function of the SLC6A4 gene.1 Numerous studies have investigated the association between 5HTTLPR and anxiety- and depression-related traits, particularly in the context of interaction with stressful life events, with conflicting2 results. The era of genome-wide association studies has generated much larger sample sizes but investigation of 5HTTLPR has been precluded, as the technology developed for high-throughput genotyping is limited to SNPs and assay of the length polymorphism is expensive and technically challenging. Likewise, 5HTTLPR genotypes are not available for samples included in the International HapMap project so that selection of SNPs that tag 5HTTLPR is not feasible from this publicly available database. Here, we use 2823 samples with both genome-wide SNP and 5HTTLPR genotypes to identify SNPs and/or SNP haplotypes that tag 5HTTLPR polymorphism.

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Authors and Affiliations

  1. Queensland Institute of Medical Research, Brisbane, QLD, Australia

    A A E Vinkhuyzen, T Dumenil, L Ryan, S D Gordon, A K Henders, G W Montgomery, N G Martin & N R Wray

  2. Washington University School of Medicine, St Louis, MO, USA

    P A F Madden & A C Heath

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  1. A A E Vinkhuyzen
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  2. T Dumenil
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  3. L Ryan
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  4. S D Gordon
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  5. A K Henders
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  6. P A F Madden
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  7. A C Heath
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  9. N G Martin
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  10. N R Wray
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Correspondence to A A E Vinkhuyzen.

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Vinkhuyzen, A., Dumenil, T., Ryan, L. et al. Identification of tag haplotypes for 5HTTLPR for different genome-wide SNP platforms. Mol Psychiatry 16, 1073–1075 (2011). https://doi.org/10.1038/mp.2011.68

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