New 'Nature' study implicates Copy Number Variations .

The most recent publication published by the AGP has generated a high profile in the media 'New Autism Genes Discovered!'.

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature09146.html

This paper has not undergone any scrutiny.

This study did not use a representative control group. The supplementary data shows that the SAGE control group (N=1880) was comprised of 31% males and 69% females, the complete opposite of the ASD group 4:1 male female ratio. The study did not control for age (as admitted by the authors) nor by IQ.

http://www.nature.com/nature/journal/vaop/ncurrent/extref/nature09146-s1.pdf

1. SAGE cohort: 1,880 control subjects from the larger SAGE case-control study were made
available. The consented sample included 31% males and 69% of females, with mean age of 39.2
(SD 9.1) and 73% of subjects self-identified as European-American, 26% as African-American
and 1% as other

Males may have a higher rate of risk for germline de novo mutations than females:

http://www.bioone.org/doi/abs/10.1111/j.1558-5646.2007.00250.x?journalCode=evol

In many instances, there are large sex differences in mutation rates, recombination rates, selection, rates of gene flow, and genetic drift. Mutation rates are often higher in males, a difference that has been estimated both directly and indirectly. The higher male mutation rate appears related to the larger number of cell divisions in male lineages but mutation rates also appear gene- and organism-specific.

The authors never explain why in heritable cases the parents are unaffected.

The controls used in this study would be unacceptable if they were used in autopsy studies.

It is time for the AGP to employ meaningful control groups that control for age, IQ and gender, this study did not meet any acceptable standards for meaningful control groups. Until they do this type of study screams out for invoking the old bromide of "correlation does not imply causation."

How do CNV's 'cause' autism? No one knows. One possible explanation has come from AIDS researchers. Aids researchers have identified a single gene (CCL31). Lower Copy number variations substantially increase the risk for infections after exposure to HIV:

http://www.sciencemag.org/cgi/content/abstract/1101160v1

The authors of the Nature study claiming CNV's "cause" autism is as big a stretch as an Aids researchers who would claim that lower CNV's in the CCL31 gene "causes" AIDS. Such an absurd claim would be immediately seized on by an unquestioning media who might come up with a catchy headline 'New AIDS Gene Discovered'.

The new IAN initiative on genetics raises a few questions. Why are blood samples not being taken from parents that may determine whether a gene variant is inherited or de novo?

Will IAN use appropriate control groups controlled for IQ and gender.

RAJ, interesting thoughts on the "New Autism Genes Discovered" article.

I just wanted to answer your question about IAN Genetics. Through IAN Genetics, we are trying to demonstrate that genetic samples can be collected quickly from many families all over the country to greatly increase the number of available samples. In the past, samples were only collected after extensive in-clinic interviews and evaluations, which meant there was high quality, first-hand data about a family, but also that it took a long time to get just one sample and cost a great deal.

Part of the problem was that autism, unlike cancer or diabetes, was not something you treat in a medical setting. It was therefore not possible for researchers to encounter people in a clinic and just ask for them to sign a research consent and get a blood sample. People with ASDs are generally not sitting around in medical facility waiting rooms.

IAN Genetics is about creating a biobank of autism samples that can be used in the future and has another advantage: the possibility of linking de-identified genetic samples with a de-identified phenotype based on IAN data. (In other words, a researcher would be able to know that this DNA sample went with a person who had Asperger's, was in a family with no other kids with ASD, had not experienced autistic regression, and had seizures which began at age 4, etc.)

It's a lack of samples that limits so much genetic research in autism, so our goal is to help rectify that. You are right that it would be even better to collect samples from parents, too. We do hope to do that at some point. Right now, we are collecting samples from a child with ASD and an unaffected sibling.