Recurrent de novo (DN) and likely gene-disruptive (LGD) mutations contribute significantly to autism spectrum disorders (ASDs) but have been primarily investigated in European cohorts. Here, we sequence 189 risk genes in 1,543 Chinese ASD probands (1,045 from trios). We report an 11-fold increase in the odds of DN LGD mutations compared with expectation under an exome-wide neutral model of mutation. In aggregate, ∼4% of ASD patients carry a DN mutation in one of just 29 autism risk genes. The most prevalent gene for recurrent DN mutations is SCN2A (1.1% of patients) followed by CHD8, DSCAM, MECP2, POGZ, WDFY3 and ASH1L. We identify novel DN LGD recurrences (GIGYF2, MYT1L, CUL3, DOCK8 and ZNF292) and DN mutations in previous ASD candidates (ARHGAP32, NCOR1, PHIP, STXBP1, CDKL5 and SHANK1). Phenotypic follow-up confirms potential subtypes and highlights how large global cohorts might be leveraged to prove the pathogenic significance of individually rare mutations.

BackgroundWe previously performed targeted sequencing of autism risk genes in probands from the Autism Clinical and Genetic Resources in China (ACGC) (phase I). Here, we expand this analysis to a larger cohort of patients (ACGC phase II) to better understand the prevalence, inheritance, and genotype–phenotype correlations of likely gene-disrupting (LGD) mutations for autism candidate genes originally identified in cohorts of European descent.MethodsWe sequenced 187 autism candidate genes in an additional 784 probands and 85 genes in 599 probands using single-molecule molecular inversion probes. We tested the inheritance of potentially pathogenic mutations, performed a meta-analysis of phase I and phase II data and combined our results with existing exome sequence data to investigate the phenotypes of carrier parents and patients with multiple hits in different autism risk genes.ResultsWe validated recurrent, LGD, de novo mutations (DNMs) in 13 genes. We identified a potential novel risk gene (ZNF292), one novel gene with recurrent LGD DNMs (RALGAPB), as well as genes associated with macrocephaly (GIGYF2 and WDFY3). We identified the transmission of private LGD mutations in genes predominantly associated with DNMs and showed that parental carriers tended to share milder autism-related phenotypes. Patients that carried DNMs in two or more candidate genes show more severe phenotypes.ConclusionsWe identify new risk genes and transmission of deleterious mutations in genes primarily associated with DNMs. The fact that parental carriers show milder phenotypes and patients with multiple hits are more severe supports a multifactorial model of risk.Electronic supplementary materialThe online version of this article (10.1186/s13229-018-0247-z) contains supplementary material, which is available to authorized users.

The aim of this study was first to investigate associations between maternal dietary patterns and autism spectrum disorders (ASDs) and second to investigate association between maternal supplement intake and ASD.We used a case-control study design to enroll typically developing (TD) children and children with ASD, and data were derived from the Autism Clinical and Environmental Database (ACED).Three seventy four children with AUTISM and 354 age matched TD children were included. The multivariate logistic regression model revealed that maternal unbalanced dietary patterns before conception had a significant increased risk of ASD in offspring (mostly meat: adjusted OR, 4.010 [95% CI, 1.080, 14.887]; mostly vegetable: adjusted OR, 2.234 [95% CI, 1.009, 4.946]); maternal supplementation of calcium during pregnancy preparation was associated with decreased ASD risk (adjusted OR, 0.480 [95% CI, 0.276, 0.836]).This study provided preliminary evidence that maternal unbalanced dietary patterns may be a risk factor for ASD and supplementation of calcium during pregnancy preparation may be inversely associated with ASD in offspring.

Background Non-suicidal self-injury (NSSI) is prevalent in adolescents and brings a series of serious consequences to their well-being. However, little is known about parents’ attitude toward NSSI in Chinese adolescents. The study aims to investigate the parents’ attitudes toward and perceptions of adolescents who have engaged in NSSI behaviors, and the impact of NSSI on their parents. Methods Purposive sampling was used in the study. The biological parents of adolescents with NSSI were recruited from the psychiatric ward of a tertiary hospital in China. Semi-structured interviews were conducted which contained three aspects, that is the history of NSSI, the process of seeking or maintaining help and the impacts on the family. Each interview typically lasted 40–50 min. All of the interviews were audio-recorded. Their responses were analyzed by the thematic analysis. Results Twenty participants completed the interview, consisting of 16 mothers and 4 fathers. Three themes and eight sub-themes were extracted: (1) the attitudes to children’s NSSI behaviors (ignorance, shame, and stereotype); (2) coping strategies of parents (the initial response to adolescents’ NSSI, and the way of help-seeking); (3) the impacts on family (altered parenting and communication styles, limited personal lives, and increased psychological pressure). Conclusion The results showed that parents lack the knowledge about NSSI and its treatment and are suffering great emotional stress. It is recommended to expand the popularization of knowledge of NSSI in adolescents and more interventions adapted to China’s sociocultural climate are required for the well-being of parents and NSSI in adolescents.

Autism spectrum disorder (ASD) describes a group of neurodevelopmental disorders with high heritability, although the underlying genetic determinants of ASDs remain largely unknown. Large-scale whole-genome studies of copy number variation in Han Chinese samples are still lacking. We performed a genome-wide copy number variation analysis of 343 ASD trios, 203 patients with sporadic cases and 988 controls in a Chinese population using Illumina genotyping platforms to identify CNVs and related genes that may contribute to ASD risk. We identified 32 rare CNVs larger than 1 Mb in 31 patients. ASD patients were found to carry a higher global burden of rare, large CNVs than controls. Recurrent de novo or case-private CNVs were found at 15q11-13, Xp22.3, 15q13.1–13.2, 3p26.3 and 2p12. The de novo 15q11–13 duplication was more prevalent in this Chinese population than in those with European ancestry. Several genes, including GRAMD2 and STAM, were implicated as novel ASD risk genes when integrating whole-genome CNVs and whole-exome sequencing data. We also identified several CNVs that include known ASD genes (SHANK3, CDH10, CSMD1) or genes involved in nervous system development (NYAP2, ST6GAL2, GRM6). Besides, our study also implicated Contactins-NYAPs-WAVE1 pathway in ASD pathogenesis. Our findings identify ASD-related CNVs in a Chinese population and implicate novel ASD risk genes and related pathway for further study.

No abstract

BackgroundLong duration of untreated psychosis (DUP) is associated with poor treatment outcome. Whether or not DUP is related to brain gray matter volume abnormalities in antipsychotic medication treatment naïve schizophrenia remains unclear at this time.MethodsPatients with treatment-naïve schizophrenia and healthy controls went through brain scan using high resolution Magnetic Resonance Imaging. DUP was evaluated using the Nottingham Onset Schedule (NOS), and dichotomized as short DUP (≤ 26 weeks) or long DUP (>26 weeks). Voxel-based methods were used for volumetric measure in the brain.ResultsFifty-seven patients (27 short DUP and 30 long DUP) and 30 healthy controls were included in the analysis. There were significant gray matter volumetric differences among the 3 groups in bilateral parahippocampus gyri, right superior temporal gyrus, left fusiform gyrus, left middle temporal gyrus, and right superior frontal gyrus (p's<0.01). Compared with healthy controls, the long DUP group had significantly smaller volume in all these regions (p's <0.05). Compared with the short-DUP group, the long-DUP group had significantly smaller volume in right superior temporal gyrus, left fusiform gyrus, and left middle temporal gyrus (p's<0.01).ConclusionOur findings suggest that DUP is associated with temporal and occipitotemporal gray matter volume decrease in treatment naïve schizophrenia. The brain structural changes in untreated psychosis might contribute to poor treatment response and long-term prognosis in this patient population.

BackgroundAutism is a neurodevelopmental disorder with an unclear etiology. Pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) have been suggested to play a role in the etiology of autism. The current study explores the associations among maternal pre-pregnancy BMI, GWG and the risk of autism in the Han Chinese population.MethodsDemographic information, a basic medical history and information regarding maternal pre-pregnancy and pregnancy conditions were collected from the parents of 705 Han Chinese children with autism and 2236 unrelated typically developing children. Binary logistic regressions were conducted to calculate the odds ratio (OR) for the relationship among pre-pregnancy BMI, GWG and the occurrence of autism. The interaction between pre-pregnancy BMI and GWG was analyzed by performing stratification analyses using a logistic model.ResultsAfter adjusting for the children’s gender, parental age and family annual income, excessive GWG was associated with autism risk in the entire sample (OR = 1.327, 95% CI: 1.021–1.725), whereas the relationship between maternal pre-pregnancy BMI and autism was not significant. According to the stratification analyses, excessive GWG increased the risk of autism in overweight/obese mothers (OR = 2.468, 95% CI: 1.102–5.526) but not in underweight or normal weight mothers.ConclusionsThe maternal pre-pregnancy BMI might not be independently associated with autism risk. However, excessive GWG might increase the autism risk of offspring of overweight and obese mothers.Electronic supplementary materialThe online version of this article (10.1186/s12888-018-1593-2) contains supplementary material, which is available to authorized users.