Association between 7q31 markers and tourette syndrome

Abstract

Tourette syndrome (TS) is a complex neuropychiatric disorder with a strong genetic basis. Although no specific susceptibility genes have been identified for TS, cytogenetic studies in selected cases suggest the existence of a predisposing gene located in the 7q31 chromosomal region. In order to test the hypothesis of a possible relationship between this region and TS at the population level, we undertook a family based association study in a sample of French Canadian patients from Quebec. For this purpose, markers D7S522, D7S523, and D7S1516 were tested using the extended transmission disequilibrium test (e-TDT). Marker D7S522 showed a biased transmission of alleles from heterozygote parents to their TS offsprings (allele-wise TDT chi(2) = 12.61, 4 df, P = 0.013, genotype-wise TDT chi(2) = 15.49, 7 df, P = 0.030). When the analysis was restricted to patients without ADHD or OCD comorbidity, similar results were observed both allele and genotype-wise (chi(2) = 10.68, 4 df, P = 0.03 and chi(2) = 12.55, 5 df, P = 0.028, respectively). In addition, marker D7S523 was also associated (allele-wise TDT chi(2) = 18.37, 7 df, P = 0.01 and genotype-wise TDT chi(2) = 46.26, 17 df, P = 0.00016), and showed a tendency for association in the comorbidity-free subgroup (genotype-wise TDT chi(2) = 18.7, 10 df, P = 0.044). Finally, marker D7S1516, contained in the inner mitochondrial membrane peptidase 2 like (IMMP2L) gene, also showed a tendency for association (genotype-wise TDT chi(2) = 32.87, 21 df, P = 0.048). These results may reflect the proximity of markers D7S522, D7S523, and possibly D7S1516 to a gene or regulatory region relevant to TS predisposition.

Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive–compulsive disorder as an example of overlapping clinical and genetic heterogeneity

“…The former is of special interest because its 7q21-q31 locus is near the chromosomal anomalies described in other cases associated with OCD and TS at 7q31 and 7q35-q36 [130][131][132]. Additionally, a family-based association study using markers in the 7q31 region demonstrated biased transmission of 7q31 marker alleles in individuals with comorbid TS, OCD and attention deficit hyperactivity disorder (ADHD) [133].…”

Altered Effect of Dopamine Transporter 3′UTR VNTR Genotype on Prefrontal and Striatal Function in Schizophrenia

“…20 This DAT 3ЈUTR VNTR has been previously associated with Parkinson disease, 21 alcoholism, 22 attention-deficit/hyperactivity disorder, 23,24 and Tourette syndrome. 25,26 Previous functional neuroimaging studies of memory paradigms in healthy subjects have reported an effect of DAT 3ЈUTR VNTR on prefrontal activation, and an additive interaction between this effect and that of a functional polymorphism for COMT (Val158Met) in prefrontal cortex. 11,[27][28][29] Nonlinear interactions between the effects of the DAT and COMT polymorphisms on hippocampal 28 and striatal 29 activation have also been reported in the context of reward and memory tasks, respectively.…”

Family-based association study of ZNF533, DOCK4 and IMMP2L gene polymorphisms linked to autism in a northeastern Chinese Han population

“…Mutations in the DOCK4 gene are associated with ovarian, prostate, and colorectal cancers, as well as glioma. Previous studies have also shown that DOCK4 is associated with Tourette's syndrome (Díaz-Anzaldúa et al, 2004) and cytogenetic aberrations (Petek et al, 2001). Genomic disruption of DOCK4 results in an additive effect and can lead to a more severe autism spectrum .…”