Autism 'caused by genetics', study suggests

[Bearware]

109. Most neurological diseases can have more than one contributory cause including my relative's Ataxia

Sorry I came on too strong. I have been meaning to respond to various posts on ASD for quite some time but
finally decided to on this one. Prior to that I was too busy posting in other worlds so I never did much DU posting.

I got leading Ataxia experts (neurologists specializing in Ataxia) to admit that my relative's Ataxia was autoimmune. I convinced them by showing them a graph of 26 gluten (specifically anti-gliadin IgG & IgA) antibody blood tests taken over 7 years along with 6 years of Ataxia motor skills tests (specifically the SARA scale). In the graph it is really obvious how the motor skills improve as the antibody levels drop below a certain level. Ataxia experts had assumed that most Sporadic (unknown cause) Ataxia cases would turn out to be genetic once they found all the mutations. After 10 years the number of Sporadic Ataxia cases is still near 50% and most of the genetic forms were found in the first dozen or so most common genetic mutations. A similar trend seems to have occurred in most of the major neurological diseases.

I have been there and been repeatedly told by experts in the genetics of the disease(s) in question that the vast majority of cases are directly caused by genetic mutations. When the studies are investigated more closely most of them only explain a chunk for 30%-40% or so as directly genetic or so with an often bigger chunk that has predisposing genes but needs some environmental trigger for disease symptoms to show.

Rates of autism increase in late-winter/early spring in higher latitude locations. This includes the US and Europe. This is on a yearly basis so when more cases are found per year, a larger percentage of them are still late-winter/early spring in higher latitude locations. This is not a pattern you would expect if the great majority of ASD cases were directly genetic.



In one of the posts above I alluded to a prior larger genetic study into ASD:

https://www.autismspeaks.org/science/science-news/largest-ever-autism-genome-study-finds-most-siblings-have-different-autism-risk

"The largest-ever autism genome study reveals that the disorder’s genetic underpinnings are even more complex than previously thought: Most siblings who have autism spectrum disorder (ASD) have different autism-linked genes."
...
"The findings challenge long-held presumptions. Because autism often runs in families, experts had assumed that siblings with the disorder were inheriting the same autism-predisposing genes from their parents. It now appears this may not be true in most cases."
...
"In the new study, the researchers sequenced 340 whole genomes from 85 families, each with two children affected by autism. They found that the majority of siblings (69 percent) had little to no overlap in the gene variations known to contribute to autism. Less than a third (31 percent) of the sibling pairs shared the same autism-associated genes."
...
"Known autism-risk genes showed up in 42 percent of the families participating in the study."



So directly genetically caused ASD only applies to 42 percent of the total and inheritance of the same genes only applies to 31%.



In a quote from the study starting this thread "Autism is almost entirely genetic in origin, new research has suggested, with between 74 and 98 per cent of cases down to biological make-up.

A study conducted by the Medical Research Council looked at 516 twins, and found that rates of Autism Spectrum Disorder (ASD) were higher in identical twins who share the same DNA."

The following is quote from the Pubmed abstract of the study:

"Design, Setting, and Participants:

We used data from the population-based cohort Twins Early Development Study, which included all twin pairs born in England and Wales from January 1, 1994, through December 31, 1996. We performed joint continuous-ordinal liability threshold model fitting using the full information maximum likelihood method to estimate genetic and environmental parameters of covariance. Twin pairs underwent the following assessments: the Childhood Autism Spectrum Test (CAST) (6423 pairs; mean age, 7.9 years), the Development and Well-being Assessment (DAWBA) (359 pairs; mean age, 10.3 years), the Autism Diagnostic Observation Schedule (ADOS) (203 pairs; mean age, 13.2 years), the Autism Diagnostic Interview-Revised (ADI-R) (205 pairs; mean age, 13.2 years), and a best-estimate diagnosis (207 pairs)."


Unless I missed it, they didn't actually look at the genes, they used an "estimate" of them with various assessments. The other study I mentioned above is whole-genome (exome) sequencing.



Why does any of this matter? In the not too distant future they will be able to treat/cure many genetic diseases with the incredible new genetic tools that are now available such as CRISPR. But for patients that do not have a direct genetic cause for their disease those tools may not work. For patients who have a direct autoimmune cause, there may be treatments available today. Failing to investigate potential autoimmune causes for any of these neurological diseases could result in years of damage that might have been avoided.

During the decade when I was dealing with Ataxia, I have had contact with a dozen or so people with the same autoimmune form. Many were not tested at all until years after first symptoms and as a result have continuing disability that might have been avoided if they were checked when they first saw a neurologist.


nomorenomore08, sorry for all the text above but you did use the term "flimsy" so I thought I should make a better case.