Evaluation of the LIM homeobox genes LHX6 and LHX8 as candidates for Tourette syndrome

P. Paschou, E. Stylianopoulou, I. Karagiannidis, R. Rizzo, Z. Tarnok, T. Wolanczyk, J. Hebebrand, M. M. Nöthen, G. Lehmkuhl, L. Farkas, P. Nagy, U. Szymanska, D. Lykidis, C. Androutsos, V. Tsironi, A. Koumoula, C. Barta, S. Klidonas, P. Ypsilantis, C. Simopoulos & 2 others G. Skavdis, M. Grigoriou

Research output: Contribution to journalArticle

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Abstract

The etiology and pathophysiology of Tourette Syndrome (TS) remain poorly understood. Multiple lines of evidence suggest that a complex genetic background and the cortico-striato-thalamo-cortical circuit are involved. The role of Lhx6 and Lhx8 in the development of the striatal interneurons, prompted us to investigate them as novel candidate genes for TS. We performed a comparative study of the expression of Lhx6 and Lhx8 and investigated genetic association with TS using two samples of trios (TSGeneSEE and German sample - 222 families). We show that Lhx6 and Lhx8 expression in the forebrain is evolutionarily conserved, underlining their possible importance in TS-related pathophysiological pathways. Our tagging-single nucleotide polymorphism (tSNP)-based association analysis was negative for association with LHX8. However, we found positive association with LHX6 in the TSGeneSEE sample (corrected P-value = 0.006 for three-site haplotype around SNP rs3808901) but no association in the sample of German families. Interestingly, the SNP allele that was identified to be significantly associated in the TSGeneSEE dataset, showed an opposite trend of transmission in the German dataset. Our analysis of the correlation of the LHX6 region with individual ancestry within Europe, revealed the fact that this particular SNP demonstrates a high degree of population differentiation and is correlated with the North to South axis of European genetic variation. Our results indicate that further study of the LHX6 gene in relation to the TS phenotype is warranted and suggest the intriguing hypothesis that different genetic factors may contribute to the etiology of TS in different populations, even within Europe.

Original languageEnglish
Pages (from-to)444-451
Number of pages8
JournalGenes, Brain and Behavior
Volume11
Issue number4
DOIs
Publication statusPublished - Jun 2012

Fingerprint

Tourette Syndrome
Homeobox Genes
Single Nucleotide Polymorphism
Corpus Striatum
Interneurons
Prosencephalon
Haplotypes
Population
Genes
Alleles
Phenotype

Keywords

  • Genetic association
  • LHX6
  • LHX8
  • Neuroanatomical expression
  • Tourette syndrome

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology

Cite this

Paschou, P., Stylianopoulou, E., Karagiannidis, I., Rizzo, R., Tarnok, Z., Wolanczyk, T., ... Grigoriou, M. (2012). Evaluation of the LIM homeobox genes LHX6 and LHX8 as candidates for Tourette syndrome. Genes, Brain and Behavior, 11(4), 444-451. https://doi.org/10.1111/j.1601-183X.2012.00778.x

Evaluation of the LIM homeobox genes LHX6 and LHX8 as candidates for Tourette syndrome. / Paschou, P.; Stylianopoulou, E.; Karagiannidis, I.; Rizzo, R.; Tarnok, Z.; Wolanczyk, T.; Hebebrand, J.; Nöthen, M. M.; Lehmkuhl, G.; Farkas, L.; Nagy, P.; Szymanska, U.; Lykidis, D.; Androutsos, C.; Tsironi, V.; Koumoula, A.; Barta, C.; Klidonas, S.; Ypsilantis, P.; Simopoulos, C.; Skavdis, G.; Grigoriou, M.

In: Genes, Brain and Behavior, Vol. 11, No. 4, 06.2012, p. 444-451.

Research output: Contribution to journalArticle

Paschou, P, Stylianopoulou, E, Karagiannidis, I, Rizzo, R, Tarnok, Z, Wolanczyk, T, Hebebrand, J, Nöthen, MM, Lehmkuhl, G, Farkas, L, Nagy, P, Szymanska, U, Lykidis, D, Androutsos, C, Tsironi, V, Koumoula, A, Barta, C, Klidonas, S, Ypsilantis, P, Simopoulos, C, Skavdis, G & Grigoriou, M 2012, 'Evaluation of the LIM homeobox genes LHX6 and LHX8 as candidates for Tourette syndrome', Genes, Brain and Behavior, vol. 11, no. 4, pp. 444-451. https://doi.org/10.1111/j.1601-183X.2012.00778.x
Paschou P, Stylianopoulou E, Karagiannidis I, Rizzo R, Tarnok Z, Wolanczyk T et al. Evaluation of the LIM homeobox genes LHX6 and LHX8 as candidates for Tourette syndrome. Genes, Brain and Behavior. 2012 Jun;11(4):444-451. https://doi.org/10.1111/j.1601-183X.2012.00778.x
Paschou, P. ; Stylianopoulou, E. ; Karagiannidis, I. ; Rizzo, R. ; Tarnok, Z. ; Wolanczyk, T. ; Hebebrand, J. ; Nöthen, M. M. ; Lehmkuhl, G. ; Farkas, L. ; Nagy, P. ; Szymanska, U. ; Lykidis, D. ; Androutsos, C. ; Tsironi, V. ; Koumoula, A. ; Barta, C. ; Klidonas, S. ; Ypsilantis, P. ; Simopoulos, C. ; Skavdis, G. ; Grigoriou, M. / Evaluation of the LIM homeobox genes LHX6 and LHX8 as candidates for Tourette syndrome. In: Genes, Brain and Behavior. 2012 ; Vol. 11, No. 4. pp. 444-451.
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