Genetic Autism Research Has Struck Out

Genetic autism research has struck out. After decades of standing at the  plate and swinging away with public and private autism research funding genetic autism research has provided little information about the nature of autism disorders, what causes them or possible treatments or cures. It is time to change batters and bring in significant funding for environmentally focused autism research. Hopefully public health authorities, Autism Speaks and others involved with distributing autism research funding will decide to give environmentally focused autism research it's long overdue turn at the plate.  

Dr. Isaac N. Pessah, Director, UC Davis Center for Children’s Environmental Health and Disease Prevention and Professor of Toxicology reviewed and summarized the overdue need for more environmental autism research in his testimony before the US Senate Committee and Public Works:

Re: State of Research on Potential Environmental Health Factors With Autism and Related Neurodevelopment Disorders

"... Although autism risk has strong heritability, no single locus alone appears to be sufficient to account for the full clinical phenotype. Results from many genomewide autism screens indicate that potential susceptibility genes are spread across the entire genome. Recently several very rare genetic mutations, single nucleotide polymorphisms (SNPs), de novo copy number variations, and epigenetic factors that influence DNA methylation were shown to contribute complexity in the transmission of autism risk. Yet genetics alone cannot account for the majority of autism cases currently being diagnosed. There is lack of full concordance between monozygotic twins, with some estimate ranging as low as 60%, and the prevalence of ASD among siblings has been reported as high as 14%. Interactions among multiple genes are likely to contribute to various types of autism, and heritable epigenetic factors and/or non-heritable environmental exposures are likely to significantly contribute to susceptibility and variable expression of autism and autism-related traits. It is therefore likely that constellations of epigenetic and environmental factors are contributing to the increasing prevalence of ASD, a rise that cannot be fully accounted for by changes in diagnostic criteria.


There is a critical need to identify environmental factors, including exposure to xenobiotic chemicals and changes in diet that contribute to autism risk and severity. The vast majority of public and private resources has, and continues, to support work on identifying genetic impairments associated with autism risk. From these studies we have learned that genetics alone cannot predict the majority of autism cases, the patterns of impairments, severity, nor can they predict success for current treatment modalities. Moreover, we have learned that many of the molecular and cellular systems that are associated with autism are the very same ones that are the target of environmental chemicals currently of concern to human health because of their widespread use. Further research is needed on modifiable factors that contribute to causing or protecting against autism. It is accepted that autism is 'multi-factorial,' meaning that there are multiple factors that combine to impair brain development. Increased efforts to identify environmental factors that contribute risk to developing autism spectrum are therefore essential to improve our understanding of the constellations of genes that confer differential sensitivity to distinct environmental exposures during gestational and neonatal development. Such approaches will likely prove useful in defining subgroups of children that differ in susceptibility to specific types of environmental exposures that promote autism risk, severity, and responsiveness to clinical and behavioral interventions.


We know that autism prevalence continues to increase dramatically clearly implicating environmental factors in autism risk. We must identify which environmental exposures and combination of exposures are contributing to increased overall risk in the population and identify the most susceptible groups. Only by bringing together the concerted effort of multidisciplinary teams of scientists can we identify which of the >80,000 commercially important chemicals currently in production promote developmental neurotoxicity consistent with the immunological and neurological impairments identified in individuals with idiopathic autism. It is clear that their is a critical need to identify which chemicals in the environment that influence the same biological pathways known to be affected in autism. Limiting exposure to these chemicals is the only way to mitigate or prevent autism in susceptible individuals."

CNTNAP2 Gene And The Unravelling Of Autism Spectrum Disorders

If anyone doubted that we are living in the era of the Autism Knowledge Revolution they should doubt no longer. The January 10 2008 edition of the American Journal of Human Genetics includes reports of three studies which separately validate the March 2006 study led by Dr. Dietrich A. Stephan, that identified a gene called CNTNAP2 which, when mutated, suggested a predisposition to autism. In Unravelling Autism Dr. Stephan comments on the three studies and states:

In this issue of AJHG, Alarcón et al.,¹ Arking et al.,² and Bakkaloglu et al.³ identify a series of functional variants in the CNTNAP2 gene that unequivocally implicate this gene as causing Type 1 autism in the general population. ...... The modern technologies and strategies derived from the Human Genome Project, coupled with the elegant sample banking, phenotyping, and data dissemination resources of groups like AGRE, are resulting, finally, in the unraveling of Autism Spectrum Disorder.

Dr. Stephan offers characteristics of Type 1 autism which many parents will recognize in their autistic children:

The three studies herein^{1, 2, 3} have moderate sample overlap and use different strategies to narrow the phenotype of the ASD cohorts to relative homogeneity before performing genotyping/resequencing across the CNTNAP2 gene locus. Nevertheless, the three studies together identify a set of common and rare variants that provide unequivocal evidence that the CNTNAP2 gene, when disrupted, leads to a subtype of ASD. This genetic subtype can be clinically characterized by ADOS/ADI-R-defined autism with language deficits and potential gender bias and parent-of-origin effects. Type 1 autism may also be associated with seizures.

The gender bias referred to by Dr. Stephan is the male gender bias associated with autism which sees from 3 to 1 to 4 to 1 male to female ratios amongst persons with autism. On the practical side Dr. Stephan indicates that the CNTNAP2 information might be of assistance in early detection and intervention in the 12 to 24 month period.

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