Lack of association between SLITRK1var321 and Tourette syndrome in a large family-based sample.
Ontology highlight
ABSTRACT:
SUBMITTER: Scharf JM
PROVIDER: S-EPMC4655203 | biostudies-literature | 2008 Apr
REPOSITORIES: biostudies-literature
Publications
Lack of association between SLITRK1var321 and Tourette syndrome in a large family-based sample.
Scharf J M JM Moorjani P P Fagerness J J Platko J V JV Illmann C C Galloway B B Jenike E E Stewart S E SE Pauls D L DL
Neurology 20080401 16 Pt 2
Similar Datasets
Project description:Recently, a genome-wide association study has indicated associations between single nucleotide polymorphisms in the Collagen Type XXVII Alpha 1 gene (COL27A1) and Tourette syndrome in several ethnic populations. To clarify the global relevance of the previously identified SNPs in the development of Tourette syndrome, the associations between polymorphisms in COL27A1 and Tourette syndrome were assessed in Chinese trios. PCR-directed sequencing was used to evaluate the genetic contributions of three SNPs in COL27A1(rs4979356, rs4979357 and rs7868992) using haplotype relative risk (HRR) and transmission disequilibrium tests (TDT) with a total of 260 Tourette syndrome trios. The family-based association was significant between Tourette syndrome and rs4979356 (TDT: χ2 = 4.804, P = 0.033; HRR = 1.75, P = 0.002; HHRR = 1.32, P = 0.027), and transmission disequilibrium was suspected for rs4979357 (TDT: χ2 = 3.969, P = 0.053; HRR = 1.84, P = 0.001; HHRR = 1.29, P = 0.044). No statistically significant allele transfer was found for rs7868992 (TDT: χ2 = 2.177, P = 0.158). Although the TDT results did not remain significant after applying the conservative Bonferroni correction (p = 0.005), the significant positive HRR analysis confirmed the possibility of showing transmission disequilibrium, which provides evidence for an involvement of COL27A1in the development of TS. However, these results need to be verified with larger datasets from different populations.
| S-EPMC4522669 | biostudies-literature
Project description:Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder that is familial and highly heritable. Although genetic influences are thought to play a significant role in the development of TS, no definite TS susceptibility genes have been identified to date. TS is believed to be genetically related to both obsessive-compulsive disorder (OCD) and grooming disorders (GD) such as trichotillomania (TTM). SAP90/PSD95-associated protein 3 (SAPAP3/DLGAP3) is a post-synaptic scaffolding protein that is highly expressed in glutamatergic synapses in the striatum and has recently been investigated as a candidate gene in both OCD and GD studies. Given the shared familial relationship between TS, OCD and TTM, DLGAP3 was evaluated as a candidate TS susceptibility gene. In a family-based sample of 289 TS trios, 22 common single nucleotide polymorphisms (SNPs) in the DLGAP3 region were analyzed. Nominally significant associations were identified between TS and rs11264126 and two haplotypes containing rs11264126 and rs12141243. Secondary analyses demonstrated that these results cannot be explained by the presence of comorbid OCD or TTM in the sample. Although none of these results remained significant after correction for multiple hypothesis testing, DLGAP3 remains a promising candidate gene for TS.
| S-EPMC3066268 | biostudies-literature
Project description:Family and twin studies provide strong evidence that genetic factors are involved in the transmission of Gilles de la Tourette syndrome (TS) and related psychiatric disorders. To detect the underlying susceptibility gene(s) for TS, we performed linkage analysis in one large French Canadian family (127 members) from the Charlevoix region, in which 20 family members were definitely affected by TS and 20 others showed related tic disorders. Using model-based linkage analysis, we observed a LOD score of 3.24 on chromosome 11 (11q23). This result was obtained in a multipoint approach involving marker D11S1377, the marker for which significant linkage disequilibrium with TS recently has been detected in an Afrikaner population. Altogether, 25 markers were studied, and, for level of significance, we derived a criterion that took into account the multiple testing arising from the use of three phenotype definitions and three modes of inheritance, a procedure that yielded a LOD score of 3.18. Hence, even after adjustment for multiple testing, the present study shows statistically significant evidence for genetic linkage with TS.
| S-EPMC1287871 | biostudies-literature
Project description:Tourette syndrome (TS) is a complex, heterozygous genetic disorder. The number of molecular genetic studies have investigated several candidate genes, particularly those implicated in the dopamine system. The dopamine D3 receptor (DRD3) gene has been considered as a candidate gene in TS. There was not any report about the association study of TS and DRD3 gene in Han Chinese population. We combined a case-control genetic association analysis and nuclear pedigrees transmission disequilibrium test (TDT) analysis to investigate the association between DRD3 gene rs6280 single nucleotide polymorphisms (SNPs) and TS in a Han Chinese population.A total of 160 TS patients was diagnosed by the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The DRD3 gene rs6280 SNPs were genotyped by TaqMan SNP genotyping assay technique in all subjects. We used a case-control genetic association analysis to compare the difference in genotype and allele frequencies between 160 TS patients and 90 healthy controls. At the same time, we used TDT analysis to identify the DRD3 gene rs6280 transmission disequilibrium among 101 nuclear pedigrees.The genotype and allele frequency of DRD3 gene rs6280 SNPs had no statistical difference between control group (90) and TS group (160) (?2 = 3.647, P = 0.161; ?2 = 0.643, P = 0.423) using Chi-squared test. At the basis of the 101 nuclear pedigrees, TDT analysis showed no transmission disequilibrium of DRD3 gene rs6280 SNPs (?2 = 0; P = 1).Our findings provide no evidence for an association between DRD3 gene rs6280 and TS in the Han Chinese population.
| S-EPMC4834778 | biostudies-literature
Project description:AimImmune system dysregulation has been implicated to play a key role in pathogenesis of Tourette syndrome (TS). IL-1α and IL-1RN are important inflammatory cytokines that mediate the inflammation. In this study, we investigated the relationship between single-nucleotide polymorphisms (SNPs) of IL-1α and IL-1RN and the susceptibility to TS in Chinese Han population.MethodsA total of 276 children with TS and their parents were recruited in the study. All DNA from our subjects were genotyped for SNPs of IL-1α rs17561 and IL-1RN rs315952 using predesigned TaqMan SNP genotyping assay. The genetic contributions of two polymorphisms were evaluated using transmission disequilibrium test (TDT) and haplotype relative risk (HRR) design. In addition, to increase the efficiency of the test, the haplotype-based HRR (HHRR) was performed.ResultsNo significant differences were observed in allelic and genotypic frequency of rs17561 in IL-1α and rs315952 in IL-1RN between the transmitted group and non-transmitted group (for IL-1α rs17561: TDT=0.890, df=1, P=0.402; HRR=1.011, X(2)=3.016, P=0.082, 95% CI=0.999-1.024; for IL-1RN rs315952: TDT=0.095, df=1, P=0.805; HRR=0.984, X(2)=0.008, P=0.929, 95% CI=0.695-1.394). Similarly, the analysis of HHRR also did not support a significant association (for IL-1α rs17561: HHRR=1.226, X(2)=0.915, P=0.339, 95% CI=0.807-1.863; for IL-1RN rs315952: HHRR=0.963, X(2)=0.094, P=0.759, 95% CI=0.758-1.225).ConclusionOur results suggest that IL-1α rs17561 and IL-1RN rs315952 polymorphisms may not be associated with susceptibility to TS in Chinese Han population. However, the results still need to be replicated in a larger sample size and different populations.
| S-EPMC4466998 | biostudies-literature
Project description:BackgroundWNK1 (With No-lysine Kinase 1) modulates numerous sodium transport-related ion channels involved in regulation of blood pressure. Several studies have indicated associations between the common variants of the WNK1 gene and hypertension or blood pressure levels. However, little data exists on Asian populations and normotensive or pre-hypertensive subjects. Our aim was to detect whether the common variations in the WNK1 gene are potential contributors to individual variations in blood pressure in a family-based sample.Material and methods525 individuals from 116 families were selected from a rural community of Northern China. Five single-nucleotide polymorphisms were selected from the WNK1 gene. Single-marker and haplotype analyses were conducted using the Family-Based Association Test program.ResultsRegretful, no associations for the 5 WNK1 SNPs and the constructed haplotype blocks of WNK1 with blood pressure level reached nominal statistical significance.ConclusionsWe conclude that although multiple candidate genes are involved in development of hypertension, the genetic polymorphism in WNK1 is not a major contributor to the observed variability in blood pressure and familial clustering risk of hypertension.
| S-EPMC4211417 | biostudies-literature
Project description:IntroductionRecurrent hypoxia, which is associated with obstructive sleep apnea syndrome (OSAS), leads to an increase in the degradation of adenosine triphosphatase into xanthine, which in turn increases uric acid concentrations.ObjectiveThe current study aimed to determine whether an association exists between OSAS and uric acid levels in the peripheral blood from a representative population of Sao Paulo (Brazil).MethodsA population-based survey adopting a probabilistic 3-stage cluster sample of Sao Paulo was used to represent the population according to gender, age, and socioeconomic class. A total of 1,042 volunteers underwent polysomnography recordings for OSAS diagnosis, blood pressure assessment, and biochemical blood analysis, and answered questionnaires.ResultsUric acid levels were correlated with most important risk factors for OSAS, such as AHI, desaturation time and index, minimum oxyhemoglobin saturation (SpO2), blood pressure, cholesterol, BMI, triglycerides and arousal, and with OSAS itself. Also, uric acid was increased in OSAS volunteers even after controlling for all confounders. Hyperuricemic volunteers presented lower mean and minimum SpO2 and increased desaturation index. Importantly, minimum SpO2 was a significant predictor of uric acid levels, which in turn was considered an independent predictor for OSAS in the binary logistic model. However, a ROC curve analysis for establishing cut-off points for uric acid levels as a biomarker of OSAS revealed moderate sensitivity and specificity.ConclusionA strong association was found between uric acid levels and OSAS in a representative sample of the population of Sao Paulo. Although they do not qualify for a biomarker alone, uric acid levels may be involved in OSAS severity and should be considered in sleep apnea management in the future.
| S-EPMC3691311 | biostudies-literature
Project description:BackgroundTourette syndrome (TS) is a childhood-onset neuropsychiatric disorder that has a unique status of a quintessentially neuropsychiatric condition at the interface of neurology (movement disorder) and psychiatry (behavioral/emotional condition). However, the behavioral and emotional profile has seemed to be neglected in the literature thus far. This study aimed to investigate the behavioral and emotional profile of TS.MethodsA total of 124 patients aged 6-16 years with TS were included in this study, including age- and sex-matched health control, attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and major depressive disorder (MDD) groups. The Child Behavior Checklist (CBCL) was used to screen the behavioral and emotional profile of the TS and other compared groups. The Yale Global Tic Severity Scale (YGTSS) was used to assess TS tic severity. Analysis of variance (ANOVA) was used to investigate the difference between the TS and other compared groups.ResultsThe results showed that the eight factors of the CBCL had no association with motor tics, vocal tics, or tic severity (p > 0.05). However, positive correlations were identified between functional impairments (subscales of YGTSS) and thought problems (TP) and rule-breaking behavior (RBB). Based on the eight-factor profile of the CBCL, TS showed a similar profile to MDD but different from ADHD and OCD, which showed similar profiles.ConclusionsBased on the assessment of the CBCL of TS, it was found that "pure" TS might show fewer behavioral and emotional problems than OCD, ADHD, and MDD. Similar behavioral and emotional profiles were identified between TS and MDD, but not OCD and ADHD. More attention needs to be paid to the thought problems and rule break problems in the CBCL in the screening stage, which might have a potential influence on the functional impairments of TS.
| S-EPMC8907575 | biostudies-literature
Project description:BackgroundGenetic factors are important in the pathogenesis of Tourette syndrome (TS). Notably, Dopamine receptor D2 (DRD2) gene has been suggested as a possible candidate gene for this disorder. Several studies have demonstrated that DRD2/ANKK1 TaqIA polymorphism is associated with an increased risk of developing TS. However, past results remain conflicting. We addressed this controversy by performing a meta-analysis of the relationship between DRD2/ANKK1 TaqIA polymorphism and TS.MethodsLiterature was searched in multiple databases including PUBMED, COCHRANE and WEB OF SCIENCE up to July 2014. The number of the genotypes for DRD2/ANKK1 TaqIA in the TS and control subjects was extracted and statistical analysis was performed using Review Manager 5.0.16 and Stata 12.0 software. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) were utilized to calculate the risk of TS with DRD2/ANKK1 TaqIA. Stratified analysis based on ethnicity was also conducted.Results523 patients with TS, 564 controls and 87 probands plus 152 relatives from five published studies were finally involved in this meta-analysis. Combined analysis revealed that the overall ORs for the DRD2/ANKK1 TaqIA A1 allele were 1.69 (95%CIs = 1.42-2.00) in the fixed-effect model and 1.66 (95%CIs = 1.33-2.08) in the random-effects model. Stratification by ethnicity indicated the TaqIA A1 allele was significantly associated with TS in Caucasians (fixed-effect model: OR=1.75, 95%CI = 1.43-2.16; random-effect model: OR=1.69, 95%CI = 1.25-2.28) and in Asians (OR=1.54, 95%CI = 1.12-2.10). Meta-analysis of the A1A1 vs. A2A2 (homozygous model), A1A2 vs. A2A2 (heterozygous model) and A1A1+A1A2 vs. A2A2 (dominant model) of this polymorphism revealed a significant association with TS in overall populations and Caucasians.ConclusionsThis meta-analysis suggested that the DRD2/ANKK1 TaqIA polymorphism might contribute to TS susceptibility, especially in Caucasian population. However, further investigation with a larger number of worldwide studies should be conducted to verify the association.
| S-EPMC4482493 | biostudies-literature
Project description:BACKGROUND:Dysbindin (DTNBP1) is a widely studied candidate gene for schizophrenia (SCZ); however, inconsistent results across studies triggered skepticism towards the validity of the findings. In this HapMap-based study, we reappraised the association between Dysbindin and SCZ in a large sample of German ethnicity. METHOD:Six hundred thirty-four cases with DSM-IV SCZ, 776 controls, and 180 parent-offspring trios were genotyped for 38 Dysbindin SNPs. We also studied two phenotypically-defined subsamples: 147 patients with a positive family history of SCZ (FH-SCZ+) and SCZ patients characterized for cognitive performance with Trail-Making Tests A and B (TMT-A: n=219; TMT-B: n=247). Given previous evidence of gene-gene interactions in SCZ involving the COMT gene, we also assessed epistatic interactions between Dysbindin markers and 14 SNPs in COMT. RESULTS:No association was detected between Dysbindin markers and SCZ, or in the FH-SCZ+ subgroup. Only one marker (rs1047631, previously reported to be part of a risk haplotype), showed a nominally significant association with performance on TMT-A and TMT-B; these findings did not remain significant after correction for multiple comparisons. Similarly, no pair-wise epistatic interactions between Dysbindin and COMT markers remained significant after correction for 504 pair-wise comparisons. CONCLUSIONS:Our results, based on one of the largest samples of European Caucasians and using narrowly-defined criteria for SCZ, do not support the etiological involvement of Dysbindin markers in SCZ. Larger samples may be needed in order to unravel Dysbindin's possible role in the genetic basis of proposed intermediate phenotypes of SCZ or to detect epistatic interactions.
| S-EPMC2856768 | biostudies-literature