title: Evaluation of the LIM homeobox genes LHX6 and LHX8 as candidates for Tourette syndrome.
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.
authors.affiliation: Department of Molecular Biology and Genetics, Democritus University of Thrace, Panepistimioupoli, Dragana, Greece. ppaschou@mbg.duth.gr
authors.forename: P
authors.initials: P
authors.lastname: Paschou
authors.forename: E
authors.initials: E
authors.lastname: Stylianopoulou
authors.forename: I
authors.initials: I
authors.lastname: Karagiannidis
authors.forename: R
authors.initials: R
authors.lastname: Rizzo
authors.forename: Z
authors.initials: Z
authors.lastname: Tarnok
authors.forename: T
authors.initials: T
authors.lastname: Wolanczyk
authors.forename: J
authors.initials: J
authors.lastname: Hebebrand
authors.forename: M M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: G
authors.initials: G
authors.lastname: Lehmkuhl
authors.forename: L
authors.initials: L
authors.lastname: Farkas
authors.forename: P
authors.initials: P
authors.lastname: Nagy
authors.forename: U
authors.initials: U
authors.lastname: Szymanska
authors.forename: D
authors.initials: D
authors.lastname: Lykidis
authors.forename: C
authors.initials: C
authors.lastname: Androutsos
authors.forename: V
authors.initials: V
authors.lastname: Tsironi
authors.forename: A
authors.initials: A
authors.lastname: Koumoula
authors.forename: C
authors.initials: C
authors.lastname: Barta
authors.forename: S
authors.initials: S
authors.lastname: Klidonas
authors.forename: P
authors.initials: P
authors.lastname: Ypsilantis
authors.forename: C
authors.initials: C
authors.lastname: Simopoulos
authors.forename: G
authors.initials: G
authors.lastname: Skavdis
authors.forename: M
authors.initials: M
authors.lastname: Grigoriou
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D007395:Interneurons / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D005879:Tourette Syndrome / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: C121947:LHX6 protein, human; C112960:LIM homeobox protein 8; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors