Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by impairments in reciprocal social interaction and communication and presence of restricted, repetitive and stereotyped patterns of behavior, interests and activities (1
). ASD is an umbrella term for Autistic Disorder, Asperger Syndrome and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) (1
). With an early onset prior to age 3 and a prevalence as high as 0.9–2.6% (2
), ASD is one of the leading causes of childhood disability and inflicts serious suffering and burden for the family and society (4
Understanding the causes of ASD is critical for developing better treatment. Twin studies have shown that the heritability of ASD is as high as 38–90%, indicating strong contributions by genetic factors as well as environmental factors (5
). The search for environmental factors has not yet led to convincing major candidates whereas the search for genes associated with autism, although far from complete or conclusive, has been more fruitful. The genes discovered so far can be roughly grouped into two categories: ‘syndromic autism related genes’ or causal genes underlying genetic disorders that cause autistic symptoms such as Fragile X Syndrome, Rett Syndrome, Tuberous Sclerosis Complex and dozens of other disorders (7
), and ‘non-syndromic autism related genes’ most of which are susceptibility genes (9
). Many experimental methods have been used to identify associated genes, including the earlier linkage analyses and low-scale candidate gene association or experimental studies as well as the more recent genome-wide association studies (GWAS), genome-wide CNV studies and expression profiling.
With hundreds of studies published, especially the recent genome-wide studies, and with the next-generation sequencing technologies providing even more power for further gene discoveries (10
), a new challenge has emerged: it has become more and more difficult for an autism researcher to answer with confidence how many genes have been associated with ASD, how strong the evidence is, what features the genes have and what pathways they involve. The amount of available literature and data and the intrinsic complexity of autism genetics demand bioinformatic data management and analysis. Three efforts have been made so far by different groups to collect genes and variations associated with ASD: AutDB (also known as SAFRI Gene) collected 219 genes (11
), Autism genetic database (AGD) collected 226 genes and 743 CNVs (13
) and Autism Chromosome Rearrangement Database (ACRD) collected 372 breakpoints and other genomic features (14
). However, they are far from a comprehensive survey of autism genetics. To bring a clearer big picture of autism genetics, we performed a comprehensive review and analysis of published literature and data, described below, resulting in a total of 2193 genes, 2806 SNPs/VNTRs, 4544 CNVs and 158 linkage regions. We provide the results as an online resource for the broader autism research community at http://autismkb.cbi.pku.edu.cn/
with extensive evidence and annotations, supporting sophisticated browsing and searching functionalities.