Genetics plays a major role in autism, but the relationships are complex and not well understood. Individuals with autism frequently also have other disorders such as fragile X syndrome, Rett syndrome and tuberous sclerosis. Mutations in specific genes — such as neuroligins, which help relay signals between neurons — have also been linked to autism.

Based on a genome-wide association study, Mark Daly of Massachusetts General Hospital and his colleagues reported in 2008 that genetic variation in the 16p11.2 chromosomal region is a major risk factor for autism. Daly and colleagues also uncovered more than 100 other rare genetic variations that appear to contribute to risk of autism, but these polymorphisms need further confirmation to prove an association with the disorder. Taking advantage of the SFARI Simplex Collection, the researchers plan to intensively sequence the implicated regions to find rare point mutations that would not be detectable using past or current genome scanning techniques.

Michael Ullman and his colleagues at Georgetown University in Washington, D.C., are examining language learning and processing in autism, with a focus on grammar acquisition. Based on previous work examining grammar and its neural underpinnings, they predicted that children with autism would show abnormalities in grammar learning.

Many of the mutations that are known to be associated with autism disable protein complexes that support the development and function of synapses — the communication junctions between neurons. Morgan Sheng and his colleagues at the Massachusetts Institute of Technology are investigating the role of these protein complexes to learn how their loss may lead to the social and cognitive disabilities in autism.

Attention deficit hyperactivity disorder (ADHD) and autism are both neurodevelopmental disorders that emerge early in life and persist. Up to half of children with an autism spectrum disorder also show marked symptoms of ADHD, and there is considerable genetic and neurobiological overlap between the two diagnoses.

In autism, tracing the connections between the underlying genes, altered brain function and behavioral symptoms is difficult because the disorder is caused by multiple factors in most people. Richard Tsien and Ricardo Dolmetsch of Stanford University in Palo Alto, California, Randall Rasmusson of the State University of New York at Buffalo and their colleagues study a form of the disorder linked to a single mutation, which may provide insights into the other forms of autism caused by many factors.

Advanced maternal and paternal age have been reported as risk factors for autism spectrum disorders. In general, the genetic quality of eggs and sperm declines over time, reducing the chance of older parents to produce normal offspring. Copy-number variation (CNV) — a type of genetic alteration commonly associated with autism spectrum disorder — is thought to be one of the most common problems with the quality of eggs or sperm in older individuals.

Early and accurate diagnosis of autism is challenging because of the paucity of biomarkers for the disorder. The neurological systems involved in social interaction — the impairment of which is a hallmark of autism spectrum disorders — offer a promising line of investigation for new biomarkers. Karen Parker and colleagues at Stanford University are undertaking the first comprehensive study to examine the relationship between oxytocin biology, one such candidate biomarker, and social impairments in individuals with autism.

16p11.2 are the most common chromosomal change seen in individuals with autism. State and his multisite team of investigators also showed that girls with autism carry evidence of more profound genetic risks, suggesting that they are protected from autism when carrying less serious mutations that would lead to autism in boys.

Unusually high levels of the signaling peptide BDNF, or brain-derived neurotrophic factor, have been detected in blood samples from children with autism. Barbara Hempstead of Weill Medical College at Cornell University and her colleagues propose that BDNF may also be over-expressed in the brains of these children, causing neurological defects that lead to the disorder.