Genome-wide linkage scan for an ethnic Han Chinese pedigree affected with schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To perform genome-wide linkage analysis for an ethnic Han Chinese pedigree with schizophrenia in order to locate the susceptibility genes.</p><p><b>METHODS</b>Genomic DNA was extracted from 4 mL of peripheral blood using conventional phenol-chloroform method. Illumina Infinium Linkage 24 BeadChips chip was used for determining the genotypes through detection of single nucleotide polymorphisms (SNPs). After processing the raw data using Illumina BeadStudio software, two-point nonparametric linkage analysis and two-point parametric linkage analysis were performed with Merlin software.</p><p><b>RESULTS</b>By two-point nonparametric linkage analysis, 27 sites with high LOD scores (LOD=0.63-0.75, P U+003C 0.05) were identified. Among these, 3 SNPs(rs993694, rs992690 rs1861577) were located in 12p12.3 region, whilst the remainders were located in 4p12-q22 region. Two-point parametric linkage analysis under a dominant model has yielded almost identical results.</p><p><b>CONCLUSION</b>Chromosomal regions 4p12-q22 and 12p12.3 probably contain susceptibility genes for schizophrenia.</p>

Association study of NOS1 gene polymorphisms and schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between nitric oxide synthase 1 (NOS1) gene polymorphisms and schizophrenia.</p><p><b>METHODS</b>Twenty eight tag single nucleotide polymorphisms (SNPs) of NOS1 in 382 schizophrenic patients and 448 healthy individuals sampled from Chinese Han population were analyzed by a Illumina GoldenGate Genotyping Assay.</p><p><b>RESULTS</b>One SNP (rs1520811) was found to be associated with schizophrenia, which however becomes negative after Bonferroni correction (P>0.05). Further analysis has failed to identify any association between particular haplotypes and the disease.</p><p><b>CONCLUSION</b>Our results did not support a significant association between NOS1 gene polymorphisms and schizophrenia.</p>

Genome-wide association study with memory measures as a quantitative trait locus for schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between gene polymorphisms and memory function through a genome-wide association study (GWAS) of schizophrenia and control group. Memory cognition was used as a quantitative trait (QT).</p><p><b>METHODS</b>Ninty-eight subjects with chronic schizophrenia and 60 matched controls were genotyped with HumanHap660 Bead Array. The results were correlated with quantitative traits including memory and memory delay.</p><p><b>RESULTS</b>Five candidate genes, including RASGRF2 (rs401758, P = 8.03×10(-5)), PLCG2 (rs7185362, P= 4.54×10(-5)), LMO1 (rs484161, P=9.80×10(-7), CSMD1 (rs2469383, P= 2.77×10(-6)) and PRKG1 (rs7898516, P=6.94×10(-5)) were associated with memory cognition deficits.</p><p><b>CONCLUSION</b>Using memory cognition as a quantitative trait, this Genome- wide association study has identified 5 susceptibility loci. With their association with nervous system development, neuronal growth, axon guidance and plasticity, brain development, above loci may play a role in the development of memory dysfunction in schizophrenia.</p>

A twin study on intelligence and processing speed heritability of children and adolescent / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the effects of the genetic and environmental factors on intelligence of children and adolescent from the Southwest China Prospective Twin Registry (SCPT).</p><p><b>METHODS</b>The intelligence was investigated by using the Wechsler Intelligence Scale for Children (C-WISC) in 333 twin pairs aged 6-16 years. The effects of genetic and environmental factors on IQ were analyzed by using structural equation modeling (SEM) and correlation analysis method. The effects in different sex and age groups in this population were also investigated.</p><p><b>RESULTS</b>Genetic influence accounted for 0.43 of total IQ variance and 0.37 of verbal IQ in 6-16 years old children and adolescent, but there was no significant genetic effect on performance IQ. The heritability of children aged 10-16 years was higher than that of those aged 6-10 years (total IQ: 0.82 vs 0.00, verbal IQ: 0.80 vs 0.00, performance IQ:0.51 vs 0.00). In males the heritability of verbal IQ (0.47) was higher than that in females (0.05). The shared environmental influences accounted fo r the majority of variance of performance IQ in both males and females.</p><p><b>CONCLUSION</b>There is moderate heritability on the total IQ and verbal IQ, while shared environmental factors played important roles on the variance of performance IQ. The heritability of IQ, verbal IQ and performance IQ are higher in older children and adolescent than that in younger children.</p>

Examining the comorbidity of attention deficit and hyperactivity disorder and conduct disorder in a population-based twin sample / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To examine three possible causes of the relationship between attention deficit and hyperactivity disorder and conduct disorder: additive genetic factors(A), common environmental factors(C) and individual-specific environmental factors(E).</p><p><b>METHODS</b>One hundred and forty pairs of twins from the Southwestern China Twin Registry were examined with the parent-rated Strength and Difficulties Questionnaire (SDQ). The cross-twin within-variable, within-twin cross-variable and cross-twin cross-variable correlations were calculated. Using structural equation modelling, bivariate models were fitted. The best fitting model was chosen based on likelihood and parsimony.</p><p><b>RESULTS</b>The observed phenotypic correlation between HYPER and COND was 0.44 (95% CI: 0.09, 0.27), with genetic factors accounting for about 70% of the observed correlation. Bivariate model fitting quantified the genetic correlation between HYPER and COND at 0.76 (95% CI: 0.31, 1) and the individual-specific environmental correlation at 0.28 (95% CI: 0.02, 0.51).</p><p><b>CONCLUSION</b>In children, three different genetic factors may exist: one that solely affects the liability to hyperactivity behaviour, one that has only an effect on conduct behaviour and one that influences both hyperactivity and conduct behaviour. Our results suggests that most of the environmental factors that increase the risk of hyperactivity behaviour do not influence conduct behaviour and vice versa.</p>

Expression of Toll-like receptors in thymus of myasthenia gravis patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the expression of Toll-like receptors (TLRs) in thymus of myasthenia gravis (MG) patients and the relationship with clinical features.</p><p><b>METHODS</b>Thymic specimens of 36 patients received extended thymectomy for MG were divided into three groups by pathological type: 13 thymoma tissues (thymoma group) and 13 thymic tissues adjacent to thymomas (parathymoma group) from 13 cases of MG patients with thymomas, and 23 thymic tissues from MG patients without thymomas (MG nonthymoma group). Twenty-one normal thymic specimens from cardiac surgery were used as controls. The levels of TLR2-4 mRNA were examined by RT-PCR, then the levels of TLR4 mRNA were assayed by real time RT-PCR and their relationship with clinical features were analyzed.</p><p><b>RESULTS</b>The levels of TLR4 mRNA among the different groups had significant differences, while there was no difference in TLR2 and TLR3 levels. The real time RT-PCR showed that the level of TLR4 mRNA in nonthymoma group was significantly higher than that in control group(0.8544+/- 0.1200 vs 0.6851+/- 0.1524, P=0.018). And so is parathymoma group compared with the thymoma group (0.8214+/- 0.1019 vs 0.7101+/- 0.0916, P=0.005). No significant difference of TLR4 mRNA level was found between the parathymoma and nonthymoma groups. Nevertheless, the expression of TLR4 in both groups was increased compared with control group. The levels of TLR4 mRNA had positive correlation with Osserman type(R=0.609; P=0.004) .</p><p><b>CONCLUSION</b>TLR4 may play a key role in the pathogenesis of MG. It was the thymic tissues adjacent to thymomas but not thymomas themselves participated in the onset of MG.</p>

Association analysis of the parkin gene in patients with sporadic Parkinson's disease from a Han population of Sichuan province / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine whether there are any associations between the -258T/G polymorphism of the promoter and the IVS3 -20T/C polymorphism in parkin gene and Parkinson's disease (PD) from a Han population in Sichuan province.</p><p><b>METHODS</b>Polymerase chain reaction (PCR), restriction fragment length polymorphism, denaturing high performance liquid chromatography(dHPLC) and sequence analysis were used to determine the genotype of each subject. The -258T/G polymorphism and IVS3 -20T/C polymorphism were analysed in 198 patients with sporadic PD and 187 healthy controls, matched for age and gender.</p><p><b>RESULTS</b>There were significant differences in allele frequency of the -258T/G polymorphism between PD patients and controls, with the G allele more common in cases than controls (52.5% vs 43.3%; chi square is 6.17, P< 0.025, OR is 1.45, 95% CI 1.04-1.86). There were also significant differences in G allele frequency between PD patients with onset age over 50 years old and controls(chi square is 9.048, P< 0.01, OR is 1.57, 95% CI:1.08-2.06). The frequency of TG+GG genotype was significantly higher in PD patients than in controls (78.79% vs 69.51%; chi square is 3.854, P< 0.05, OR is 1.63, 95% CI:0.88-2.38). In addition, there were significant differences in age of onset between PD patients with different genotypes (P< 0.05). The average age of onset in group of GG genotype was later about 5 years compared with the group of TT or TG genotype. The frequency of CC genotype in IVS3 -20T/C polymorphism was much higher than that of TC genotype. No TT genotype was found.</p><p><b>CONCLUSION</b>This study suggests that the parkin promoter -258T/G polymorphism might be a risk factor for late onset PD in Sichuan. CC genotype for IVS3 -20T/C polymorphism is common in Sichuan Han population. No TT genotype for IVS3 -20T/C polymorphism is found in Sichuan Han population.</p>