Distribution patterns of the two genetic groups of Corbicula fluminea in a lotic-lentic system.

Differences in local habitat conditions are often implicated as drivers for morphological and genetic divergence in natural populations. However, there are still relatively few studies regarding how divergent habitats influence patterns for morphotypes and genetic lineages in aquatic invertebrates. In this study, we explored the morphological patterns, genetic divergence, and distributions of a bivalve, Corbicula fluminea, in a lotic-lentic system. Sampling locations included lotic, ecotone, and lentic habitats. First, we found two lineages (Lineages A and B) with significant genetic divergence that primarily corresponded to two morphotypes (Morphs D and C) of C. fluminea. Lineage A consisted of 88.68% Morph D (shell sculpture: 8-14 ridges/cmsh) and 11.32% Morph C (shell sculpture: 15 ridges/cmsh) individuals and had genetic similarity to invasive populations. Lineage B consisted of only Morph C (shell sculpture: 15-23 ridges/cmsh). Second, we revealed clear effects of habitat on the spatial distribution patterns for the two lineages of C. fluminea. Lineage A was dominant in lotic habitats, with a significantly higher density than that of Lineage B in these locations. Lineage B was dominant in lentic habitats. However, both lineages had their highest densities in the ecotone habitat, without clear dominance and no significant difference in density between groups. Individuals of Lineages A and B are different in shell morphology, which may be related to a benefit trade-off between shell shapes that allow for rapid burrowing and holding position in different flow conditions. The distribution patterns indicate that Lineages A and B may not prefer uniquely lotic and lentic habitats, but each lineage is more tolerant to one habitat type, respectively. Generally, our study established a correlation among morphotypes, lineages, and different habitats for C. fluminea along a lotic-lentic gradient system, which has important implementations for fisheries management units and for understanding the role of habitat preference for this species in monitoring for pioneer dispersal in invasive species management.

Replication of previous autism-GWAS hits suggests the association between NAA1, SORCS3, and GSDME and autism in the Han Chinese population.

Background: Autism is a severe neurodevelopmental disorder characterized by social interaction deficits, impairments in communication, and restricted and repetitive stereotyped behavior and activities. Family and twin studies suggested an essential role of genetic factors in the etiology of autism spectrum disorder (ASD). Also, other studies found SORCS3 and GSDME (DFNA5) might be involved in brain development and susceptible to ASD. Methods: In this study, 17 genome-wide significant SNPs reported in previous ASD genome-wide association studies (GWAS) and 7 SNPs in strong linkage disequilibrium with known ASD GWAS hits were selected to investigate the association between these SNPs and autism in the Han Chinese population. Then, 10 tagSNPs in SORCS3 and 11 tagSNPs in GSDME were selected to analyze the association between these SNPs and autism. The selected 24 SNPs and tagSNPs were genotyped using the Agena MassARRAY SNP genotyping assay in 757 Han Chinese autism trios. Results: Rs1484144 in NAA11 was significantly associated with autism; significance remained after the Bonferroni correction (P < 0.0022). Also, rs79879286, rs12154597, and rs12540919 near GSDME, as well as rs9787523 and rs3750261 in SORCS3, were nominally associated with autism. Conclusion: Our study suggests that rs1484144 in NAA11 is a significant SNP for autism in the Han Chinese population, while SORCS3 and GSDME might be the susceptibility genes for autism in this population.

Comparison of the Clancy Autism Behavior Scale and Autism Behavior Checklist for Screening Autism Spectrum Disorder.

PURPOSE: To make early detection of individuals with autism spectrum disorder (ASD), caregiver-report instruments remain an efficient and adaptable option for the preliminary assessment. This study aimed to compare the psychometric properties of the Clancy Autism Behavior Scale (CABS) and Autism Behavior Checklist (ABC) as screening tools for ASD by caregivers. METHODS: The data were collected from 154 pairs of children and their parents, who sought medical attention for suspected autism at Peking University Sixth Hospital. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, Youden index, and area under the receiver operating characteristics curves (AUC) of the CABS and ABC were calculated and compared using recommended cut-off values from initial papers. The optimal cut-off values for CABS and ABC were determined according to the maximum Youden index. RESULTS: The ABC performed better than the CABS in screening autistic persons. Specifically, the ABC demonstrated higher sensitivity than the CABS in identifying children with ASD, while the CABS exhibited superior specificity compared to the ABC. According to the maximum Youden index, the optimal cut-off value was determined to be 13 for CABS and 62 for ABC. CONCLUSION: The ABC exhibits higher sensitivity and overall performance in screening individuals with ASD compared to the CABS. The ABC is more suitable as a screening tool for caregivers in both domestic and clinical settings, while the CABS may be utilized when evaluation time or medical resources are limited due to its shorter completion time and fewer items.

A brain structural connectivity biomarker for autism spectrum disorder diagnosis in early childhood.

Background: Autism spectrum disorder (ASD) is associated with altered brain development, but it is unclear which specific structural changes may serve as potential diagnostic markers, particularly in young children at the age when symptoms become fully established. Furthermore, such brain markers need to meet the requirements of precision medicine and be accurate in aiding diagnosis at an individual rather than only a group level. Objective: This study aimed to identify and model brain-wide differences in structural connectivity using diffusion tensor imaging (DTI) in young ASD and typically developing (TD) children. Methods: A discovery cohort including 93 ASD and 26 TD children and two independent validation cohorts including 12 ASD and 9 TD children from three different cities in China were included. Brain-wide (294 regions) structural connectivity was measured using DTI (fractional anisotropy, FA) together with symptom severity and cognitive development. A connection matrix was constructed for each child for comparisons between ASD and TD groups. Pattern classification was performed on the discovery dataset and the resulting model was tested on the two independent validation datasets. Results: Thirty-three structural connections showed increased FA in ASD compared to TD children and associated with both autistic symptom severity and impaired general cognitive development. The majority (29/33) involved the frontal lobe and comprised five different networks with functional relevance to default mode, motor control, social recognition, language and reward. Overall, classification achieved very high accuracy of 96.77% in the discovery dataset, and 91.67% and 88.89% in the two independent validation datasets. Conclusions: Identified structural connectivity differences primarily involving the frontal cortex can very accurately distinguish novel individual ASD from TD children and may therefore represent a robust early brain biomarker which can address the requirements of precision medicine.

Associations of essential element serum concentrations with autism spectrum disorder.

This case-control study explored the associations between autism spectrum disorder (ASD) and the serum concentration of nine chemical elements in children. The study recruited 92 Chinese children with ASD and 103 typically developing individuals. Serum concentrations of nine chemical elements (calcium, iodine, iron, lithium, magnesium, potassium, selenium, strontium, and zinc) were determined by inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectrometry (ICP-AES). An unconditional logistic regression model was used to analyze the associations between the serum concentrations of the elements and the risk of ASD. After adjusting for confounders, the multivariate analysis results showed that zinc ≤ 837.70 ng/mL, potassium > 170.06 µg/mL, and strontium ≤ 52.46 ng/mL were associated with an increased risk of ASD, while selenium > 159.80 ng/mL was associated with a decreased risk of ASD. Furthermore, the degree of lithium and zinc deficiency was associated with ASD severity. The results indicated that metallomic profiles of some specific elements might play important roles in the development of ASD, a finding of scientific significance for understanding the etiology, and providing dietary guidance for certain ASD types.

Altered Expression of Brain-specific Autism-Associated miRNAs in the Han Chinese Population.

Autism is a complex neurodevelopmental disorder. However, its etiology is still unknown. MicroRNAs (miRNAs) are key post-transcriptional regulators. They play an important role in neurodevelopment and brain functions and may be involved in the pathogenesis of autism. Previous studies indicated altered expression of miRNAs in patients with autism. However, the findings were not consistent, and further explorations were needed. This study aimed to investigate whether miRNAs were dysregulated in autism. We examined the expression of 30 brain-specific autism-associated miRNAs in 110 patients with autism and 113 controls in the Han Chinese population using quantitative reverse transcription-polymerase chain reaction. The results demonstrated that 10 miRNAs (hsa-miR-191-5p, hsa-miR-151a-3p, hsa-miR-139-5p, hsa-miR-181a-5p, hsa-miR-432-5p, hsa-miR-181b-5p, hsa-miR-195-5p, hsa-miR-328-3p, hsa-miR-106a-5p, and hsa-miR-484) were significantly differentially expressed (false discovery rate <0.05). All of them were up-regulated in patients with autism compared with controls. The targets of these miRNAs were enriched for genes and pathways related to neurodevelopment, brain functions and autism. These findings suggested the participation of these 10 miRNAs in the pathogenesis of autism in the Han Chinese population.

Family-based association study identifies SNAP25 as a susceptibility gene for autism in the Han Chinese population.

Autism is a neurodevelopmental disorder with high heritability. Synaptosome associated protein 25 (SNAP25) encodes a presynaptic membrane-binding protein. It plays a crucial role in neurotransmission and may be involved in the pathogenesis of autism. However, the association between SNAP25 and autism in the Han Chinese population remains unclear. To investigate whether single nucleotide polymorphisms (SNPs) in SNAP25 contribute to the risk of autism, we performed a family-based association study of 14 tagSNPs in SNAP25 in 640 Han Chinese autism trios. Our results demonstrated that rs363018 in SNAP25 was significantly associated with autism under both additive (A > G, Z = 3.144, P = .0017) and recessive models (A > G, Z = 3.055, P = .0023) after Bonferroni correction (P < .0036). An additional SNP, rs8636, was nominally associated with autism under the recessive model (C > T, Z = 1.972, P = .0487). Haplotype-based association test revealed that haplotypes A-T (Z = 2.038, P = .0415) and G-T (Z = -3.114, P = .0018) of rs363018-rs362582 were significantly associated with autism after the permutation test (P = .0158). These findings suggest that SNAP25 may represent a susceptibility gene for autism in the Han Chinese population.

Family-based association study of ZNF804A polymorphisms and autism in a Han Chinese population.

BACKGROUND: Autism is a complex neurodevelopmental disorder with high heritability. Zinc finger protein 804A (ZNF804A) was suggested to play important roles in neurodevelopment. Previous studies indicated that single-nucleotide polymorphism (SNP) rs1344706 in ZNF804A was strongly associated with schizophrenia and might influence social interaction. Only one study explored the significance of ZNF804A polymorphisms in autism, which discovered that rs7603001 was nominally associated with autism. Moreover, no previous study investigated the association between ZNF804A and autism in a Han Chinese population. Here, we investigated whether these two SNPs (rs1344706 and rs7603001) in ZNF804A contribute to the risk of autism in a Han Chinese population. METHODS: We performed a family-based association study in 640 Han Chinese autism trios. Sanger sequencing was used for sample genotyping. Then, single marker association analyses were conducted using the family-based association test (FBAT) program. RESULTS: No significant association was found between the two SNPs (rs1344706 and rs7603001) in ZNF804A and autism (P > 0.05). CONCLUSIONS: Our findings suggested that rs1344706 and rs7603001 in ZNF804A might not be associated with autism in a Han Chinese population.

Association between CNTNAP2 polymorphisms and autism: A family-based study in the chinese han population and a meta-analysis combined with GWAS data of psychiatric genomics consortium.

Autism is a childhood neuropsychiatric disorder with evidence of a strong genetic component in the complex etiologies. Contactin-associated protein-like 2 (CNTNAP2), a member of the neurexin superfamily, plays an essential role in neural development. CNTNAP2 was considered as one of the most susceptible genes for autism spectrum disorder (ASD). Some studies indicated the association of CNTNAP2 with ASD, while others reported no association. Given the inconsistent results of the previous studies, we performed a family-based association study between 9 single-nucleotide polymorphisms (SNPs) of CNTNAP2 and autism in 640 autistic trios in the Chinese Han population. Then, an updated meta-analysis, combined with the data from Psychiatric Genomics Consortium (iPSYCH-PGC ASD, 2017) and available association studies, was conducted. No SNPs were significantly associated with autism in the Chinese Han population. In the meta-analysis, the two frequently reported SNPs (rs2710102 and rs7794745) showed no significant association with ASD. Therefore, CNTNAP2 polymorphisms might not be associated with autism. Autism Research 2019, 12: 553-561. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In present family-based association study, no single-nucleotide polymorphisms (SNPs) were significantly associated with autism in the Chinese Han population. In the updated meta-analysis, the association between the two frequently reported SNPs (rs2710102 and rs7794745) in CNTNAP2 and the risk of ASD was explored. However, the results showed no significant association. Therefore, our study suggested that CNTNAP2 polymorphisms might not be associated with autism.

Replication of previous GWAS hits suggests the association between rs4307059 near MSNP1AS and autism in a Chinese Han population.

Autism is a complex neurodevelopmental disorder with high heritability. Previous genome-wide association studies (GWAS) demonstrated that some single-nucleotide polymorphisms (SNPs) were significantly associated with autism, while other studies focusing on these GWAS hits showed inconsistent results. Besides, the association between these variants and autism in the Chinese Han population remains unclear. Therefore, this family-based association study was performed in 640 Chinese Han autism trios to investigate the association between autism and 7 SNPs with genome-wide significance in previous GWAS (rs4307059 near MSNP1AS, rs4141463 in MACROD2, rs2535629 in ITIH3, rs11191454 in AS3MT, rs1625579 in MIR137HG, rs11191580 in NT5C2, and rs1409313 in CUEDC2). The results showed a nominal association between the T allele of rs4307059 and autism under both additive model (T>C, Z = 2.250, P = .024) and recessive model (T>C, Z = 2.109, P = .035). The findings provided evidence that rs4307059 near MSNP1AS might be a susceptibility variant for autism in the Chinese Han population.

Association study and mutation sequencing of genes on chromosome 15q11-q13 identified GABRG3 as a susceptibility gene for autism in Chinese Han population.

Cytogenetic studies suggested that chromosome 15q11-q13 might be a candidate region that increases the risk of autism. Previous association studies in Caucasian populations identified the risk variants of genes in this region. However, the association of these genes with autism in Chinese Han population remains unclear. Herein, 512 autism trios were utilized for a family-based association study of 41 tag single nucleotide polymorphisms (SNPs) in this region to explore the association between protein-coding genes on chromosome 15q11-q13 and autism in Chinese Han population. Furthermore, we sequenced these autism-related genes to detect rare variants in 512 autism trios and 575 healthy controls. Our results showed that the C allele of rs7180500 in GABRG3 was a risk variant for autism (p = 0.00057). The expression quantitative trait loci (eQTL) analysis revealed that the C allele of rs7180500 might be associated with the expression of GABRG3 in the cerebellum (Braineac: p = 0.0048; GTEx: p = 0.0010). Moreover, the sequencing identified two rare variants rs201602655 (p.Val233Met) and rs201427468 (p.Pro365Ser) in GABRG3 and six rare variants in GABRB3 in autistic patients. Among these variants, rs201602655 (p.Val233Met) in GABRG3 were observed in 9 of 512 autistic children and 2 of 575 healthy controls (Pearson χ2-test, χ2 = 5.375, p = 0.020). The functional prediction indicated that rs201602655 (p.Val233Met) might be deleterious. Thus, these findings demonstrated that GABRG3 might contribute to the pathogenesis of autism in Chinese Han population.

Genetic variants in the transcription regulatory region of MEGF10 are associated with autism in Chinese Han population.

Multiple epidermal growth factor-like-domains 10 (MEGF10), a critical member of the apoptotic engulfment pathway, mediates axon pruning and synapse elimination during brain development. Previous studies indicated that synaptic pruning deficit was associated with autism-related phenotypes. However, the relationship between MEGF10 and autism remains poorly understood. Disease-associated variants are significantly enriched in the transcription regulatory regions. These include the transcription start site (TSS) and its cis-regulatory elements. To investigate the role of MEGF10 variants with putative transcription regulatory function in the etiology of autism, we performed a family-based association study in 410 Chinese Han trios. Our results indicate that three single nucleotide polymorphisms (SNPs), rs4836316, rs2194079 and rs4836317 near the TSS are significantly associated with autism following Bonferroni correction (p = 0.0011, p = 0.0088, and p = 0.0023, respectively). Haplotype T-A-G (rs4836316-rs2194079-rs4836317) was preferentially transmitted from parents to affected offspring (p permutation = 0.0055). Consistently, functional exploration further verified that the risk allele and haplotype might influence its binding with transcription factors, resulting in decreased transcriptional activity of MEGF10. Our findings indicated that the risk alleles and haplotype near the MEGF10 TSS might modulate transcriptional activity and increase the susceptibility to autism.

A Volumetric and Functional Connectivity MRI Study of Brain Arginine-Vasopressin Pathways in Autistic Children.

Dysfunction of brain-derived arginine-vasopressin (AVP) systems may be involved in the etiology of autism spectrum disorder (ASD). Certain regions such as the hypothalamus, amygdala, and hippocampus are known to contain either AVP neurons or terminals and may play an important role in regulating complex social behaviors. The present study was designed to investigate the concomitant changes in autistic behaviors, circulating AVP levels, and the structure and functional connectivity (FC) of specific brain regions in autistic children compared with typically developing children (TDC) aged from 3 to 5 years. The results showed: (1) children with ASD had a significantly increased volume in the left amygdala and left hippocampus, and a significantly decreased volume in the bilateral hypothalamus compared to TDC, and these were positively correlated with plasma AVP level. (2) Autistic children had a negative FC between the left amygdala and the bilateral supramarginal gyri compared to TDC. The degree of the negative FC between amygdala and supramarginal gyrus was associated with a higher score on the clinical autism behavior checklist. (3) The degree of negative FC between left amygdala and left supramarginal gyrus was associated with a lowering of the circulating AVP concentration in boys with ASD. (4) Autistic children showed a higher FC between left hippocampus and right subcortical area compared to TDC. (5) The circulating AVP was negatively correlated with the visual and listening response score of the childhood autism rating scale. These results strongly suggest that changes in structure and FC in brain regions containing AVP may be involved in the etiology of autism.

The Use of Linguistic Cues in Sentence Comprehension by Mandarin-Speaking Children with High-Functioning Autism.

Two studies were conducted to investigate how high-functioning children with autism use different linguistic cues in sentence comprehension. Two types of linguistic cues were investigated: word order and morphosyntactic cues. The results show that children with autism can use both types of cues in sentence comprehension. However, compared to age-matched typically developing peers, children with autism relied significantly more on word order cues and exhibited significantly more difficulties in interpreting sentences in which there was a conflict between the morphosyntactic cue and the word order cue. We attribute the difficulties exhibited by children with autism to their deficits in executive function. We then discuss the implications of the findings for understanding the nature of the sentence processing mechanism in autism.

Association of oligodendrocytes differentiation regulator gene DUSP15 with autism.

OBJECTIVES: Autism is a pervasive neurodevelopmental disorder with high heritability. Genetic factors play crucial roles in the aetiology of autism. Dual specificity phosphatase 15 (DUSP15) has been recognised as a key regulator gene for oligodendrocytes differentiation. A previous study detected one de novo missense variant (p.Thr107Met) with probable deleterious function in exon 6 of DUSP15 among patients with autism. Therefore, we sequenced this mutation in autistic children and performed an association analysis between DUSP15 polymorphisms and autism. METHODS: We performed a case-control study between 255 children affected with autism and 427 healthy controls. Four tag-single nucleotide polymorphisms (SNPs) were selected. These SNPs and the previously reported mutation in exon 6 of DUSP15 were genotyped via Sanger sequencing. RESULTS: Our results showed that rs3746599 was significantly associated with autism under allelic, additive and dominant models, respectively (χ2 = 9.699, P = 0.0018; χ2 = 16.224, P = 0.001; χ2 = 7.198, P = 0.007). The association remained significant after Bonferroni correction and permutation tests (n = 10,000). We did not detect the missense variant p.Thr107Met reported in previous studies. However, a de novo missense variant of DUSP15 (p.Ala56Thr) with a probable disease-causing effect was detected in one autistic child while absent in healthy controls. CONCLUSIONS: Our findings initially suggest that DUSP15 might be a susceptibility gene for autism in Chinese Han population.

Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms.

Autism spectrum disorder (ASD) is defined by impairments of social interaction and the presence of obsessive behaviors. The "twin" nonapeptides oxytocin (OXT) and arginine-vasopressin (AVP) are known to play regulatory roles in social behaviors. However, the plasma levels and behavioral relevance of OXT and AVP in children with ASD have seldom been investigated. It is also unknown whether their mothers have abnormal plasma peptide levels. Here, using well-established methods of neuropeptide measurement and a relatively large sample size, we determined the plasma levels of the two neuropeptides in 85 normal children, 84 children with ASD, and 31 mothers from each group of children. As expected, children with ASD had lower plasma OXT levels than gender-matched controls (P = 0.028). No such difference was found for plasma AVP concentrations. Correlation analysis showed that ASD children with higher plasma OXT concentrations tended to have less impairment of verbal communication (Rho = -0.22, P = 0.076), while those with higher plasma AVP levels tended to have lower levels of repetitive use of objects (Rho = -0.231, P = 0.079). Unlike the findings in children, maternal plasma OXT levels showed no group difference. However, plasma AVP levels in the mothers of ASD children tended to be lower than in the mothers of normal children (P = 0.072). In conclusion, our results suggest that the OXT system is dysregulated in children with ASD, and that OXT and AVP levels in plasma seem to be associated with specific autistic symptoms. The plasma levels of OXT or AVP in mothers and their ASD children did not seem to change in the same direction.

Chromatin remodeling gene EZH2 involved in the genetic etiology of autism in Chinese Han population.

Autism spectrum disorder (ASD) is a group of severe neurodevelopmental disorders. Epigenetic factors play a critical role in the etiology of ASD. Enhancer of zest homolog 2 (EZH2), which encodes a histone methyltransferase, plays an important role in the process of chromatin remodeling during neurodevelopment. Further, EZH2 is located in chromosome 7q35-36, which is one of the linkage regions for autism. However, the genetic relationship between autism and EZH2 remains unclear. To investigate the association between EZH2 and autism in Chinese Han population, we performed a family-based association study between autism and three tagged single nucleotide polymorphisms (SNPs) that covered 95.4% of the whole region of EZH2. In the discovery cohort of 239 trios, two SNPs (rs740949 and rs6464926) showed a significant association with autism. To decrease false positive results, we expanded the sample size to 427 trios. A SNP (rs6464926) was significantly associated with autism even after Bonferroni correction (p=0.008). Haplotype G-T (rs740949 and rs6464926) was a risk factor for autism (Z=2.655, p=0.008, Global p=0.024). In silico function prediction for SNPs indicated that these two SNPs might be regulatory SNPs. Expression pattern of EZH2 showed that it is highly expressed in human embryonic brains. In conclusion, our findings demonstrate that EZH2 might contribute to the genetic etiology of autism in Chinese Han population.

Genetic Evidence for Possible Involvement of the Calcium Channel Gene CACNA1A in Autism Pathogenesis in Chinese Han Population.

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders. Recent studies suggested that calcium channel genes might be involved in the genetic etiology of ASD. CACNA1A, encoding an alpha-1 subunit of voltage-gated calcium channel, has been reported to play an important role in neural development. Previous study detected that a single nucleotide polymorphism (SNP) in CACNA1A confers risk to ASD in Central European population. However, the genetic relationship between autism and CACNA1A in Chinese Han population remains unclear. To explore the association of CACNA1A with autism, we performed a family-based association study. First, we carried out a family-based association test between twelve tagged SNPs and autism in 239 trios. To further confirm the association, the sample size was expanded to 553 trios by recruiting 314 additional trios. In a total of 553 trios, we identified association of rs7249246 and rs12609735 with autism though this would not survive after Bonferroni correction. Our findings suggest that CACNA1A might play a role in the etiology of autism.

Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a strong genetic component. Many lines of evidence indicated that ASD shares common genetic variants with other psychiatric disorders (for example, schizophrenia). Previous studies detected that calcium channels are involved in the etiology of many psychiatric disorders including schizophrenia and autism. Significant association between CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit) and schizophrenia was detected. Furthermore, rare mutation in CACNA1C is suggested to cause Timothy syndrome, a multisystem disorder including autism-associated phenotype. However, there is no evidence for association between CACNA1C and autism in Chinese Han population. To investigate the association between single nucleotide polymorphisms (SNP) in CACNA1C and autism, we first performed a family-based association study between eighteen SNPs in CACNA1C and autism in 239 trios. All SNPs were genotyped by using Sequenom genotyping platform. Two SNPs (rs1006737 and rs4765905) have a trend of association with autism. To further confirm the association between these two SNPs with autism, we expanded the sample size to 553 trios by adding 314 trios. Association analyses for SNPs and haplotype were performed by using family-based association test (FBAT) and Haploview software. Permutation tests were used for multiple testing corrections of the haplotype analyses (n=10,000). The significance level for all statistical tests was two-tailed (p<0.05). The results demonstrated that G allele of rs1006737 and G allele of rs4765905 showed a preferential transmission to affected offspring in 553 trios (p=0.035). Haplotype analyses showed that two haplotypes constructed from rs1006737 and rs4765905 were significantly associated with autism (p=0.030, 0.023, respectively; Global p=0.046). These results were still significant after permutation correction (n=10,000, p=0.027). Our research suggests that CACNA1C might play a role in the genetic etiology of autism in Chinese Han population.

The use of grammatical morphemes by Mandarin-speaking children with high functioning autism.

The present study investigated the production of grammatical morphemes by Mandarin-speaking children with high functioning autism. Previous research found that a subgroup of English-speaking children with autism exhibit deficits in the use of grammatical morphemes that mark tense. In order to see whether this impairment in grammatical morphology can be generalised to children with autism from other languages, the present study examined whether or not high-functioning Mandarin-speaking children with autism also exhibit deficits in using grammatical morphemes that mark aspect. The results show that Mandarin-speaking children with autism produced grammatical morphemes significantly less often than age-matched and IQ-matched TD peers as well as MLU-matched TD peers. The implications of these findings for understanding the grammatical abilities of children with autism were discussed.