Autism screening closer as 100 genes linked to disorder are identified

[Bob]

Autism screening closer as 100 genes linked to disorder are identified
A 10 year study examining the DNA of thousands of children with autism has found 100 gene mutations which are responsible for the disorder
The Daily Telegraph (UK)
29 Oct 2014
http://www.telegraph.co.uk/science/...-genes-linked-to-disorder-are-identified.html

Screening for autism could be a step closer after more than 100 gene mutations which could cause the disorder were identified by scientists.

Great Ormond Street Hospital and US researchers have been working to find the genetic blueprint of autism for the last 10 years.

After studying DNA samples from children they found than 100 genes which might account for the disorder, and significantly they were discovered they were also present in their parents suggesting autism is inherited.

Read more here:
http://www.telegraph.co.uk/science/...-genes-linked-to-disorder-are-identified.html

 

[Bob]

Also, there's a BBC article here:

Study points to new genetic risks for autism
BBC News
30 October 2014
http://www.bbc.co.uk/news/health-29819746

A massive international study has started to unpick the "fine details" of why some people develop autism, researchers have said.

They looked at thousands of DNA samples from children with autism and their parents.

The results, in the journal Nature, linked 33 genes to the condition with many involved in brain development.

Read more here:
http://www.bbc.co.uk/news/health-29819746

 

[Bob]

I think this is the paper referred to, published in Nature...

Synaptic, transcriptional and chromatin genes disrupted in autism
De Rubeis et al.
Nature
doi:10.1038/nature13772
Published online 29 October 2014
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13772.html

Abstract:
The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability–transcription coupling, as well as histone-modifying enzymes and chromatin remodellers—most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.

 

[natasa778]

Most likely a red herring ... i.e. not causative (or even risk-forming) but simply a consequence of longer genes being more at risk of mutations, as with cancer

http://scienceoveracuppa.com/2013/06/30/all-roads-once-led-to-rome-but-do-all-roads-lead-to-autism/

... So what does this mean? As Lawrence et al. suggest, OR and large genes may have higher rates of mutation in general. Therefore, specific precautions need to be taken in scientific analysis to account for the varying rates of mutations across genes in order to avoid false positives in cancer research. They state quite clearly that they believe a large number of genes which have reportedly been associated with various types of cancers are in fact not causally related to the conditions but are, in short, coincidental. Especially in the case of a disease like cancer which is characterized by a progressively disturbed and destabilized genome.

Autism. What does autism have to do with cancer? At the moment, my ideas are still somewhat vague. However, I suspect it isn’t coincidence that those findings which predict false positives in the Lawrence et al. study are also extremely common in autism.

What needs to be looked at imo is WHY the activation of mobile elements in parents/germline/embrio is happening, only then can we start talking about risk

 

[natasa778]

ps have a look at this one on mice and man http://www.businessinsider.com/algae-virus-may-be-changing-cognitive-ability-2014-10#ixzz3HiQmoGGJ

 

[taniaaust1]

I think this is the paper referred to, published in Nature...

Synaptic, transcriptional and chromatin genes disrupted in autism
De Rubeis et al.
Nature
doi:10.1038/nature13772
Published online 29 October 2014
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13772.html

. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability–transcription coupling, as well as histone-modifying enzymes and chromatin remodellers—most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.

Very interesting as I have Aspergers and Valentijns program which picks out the more uncommon gene mutations we have.. a had quite a few double copy ones to do with lysine

 

[Sidereal]

The prevalence of autism spectrum disorders has been rising rapidly in recent decades. Clearly the most important risk factors must be environmental. By environmental I don't mean to imply refrigerator mother or other psychoquackery. I'm talking infections, toxins, diet, antibiotics etc.

The Nature abstract doesn't say what the effect sizes are for these genes (likely abysmal). In general, genetic research has been a total failure in the study of neuropsychiatric disorders and has brought us no closer to better prevention and treatment. An incredible amount of money has been spent on genetic research of this sort. Everyone can judge for themselves if it has led to any therapeutic breakthroughs for autism, schizophrenia, mood disorders, Alzheimer's, Parkinson's, MS, ALS etc.

 

[Valentijn]

Most likely a red herring ... i.e. not causative (or even risk-forming) but simply a consequence of longer genes being more at risk of mutations, as with cancer

Yeah, C alleles like to degrade T alleles as a natural matter of course, so it really isn't odd to find some de novo (non-inherited) mutations. It's a bit more interesting if a large number of patients are sharing the same mutations, de novo or otherwise, when compared to controls. A rate of 5% of patients having a mutation is not impressive unless we also have similar data for controls.

And when someone says they found 107 relevant genes, it really sounds like they found a bunch of tiny effects and might or might not have made statistical corrections to account for looking at so many SNPs.

 

[Bob]

The prevalence of autism spectrum disorders has been rising rapidly in recent decades. Clearly the most important risk factors must be environmental. By environmental I don't mean to imply refrigerator mother or other psychoquackery. I'm talking infections, toxins, diet, antibiotics etc.

I'm not too familiar with aspergers/autism research, and I wonder if aspergers/autism rates are actually rising, or whether perhaps it's just recognition and diagnosis that are improving, along with better statistics gathering?

Years ago, many people with high-functioning aspergers/autism would not have had any diagnosis whatsoever, and many with autism may not have had been recognised as having autism but may have been given some other vague label.

Perhaps it's a bit like when some people say that ME/CFS is a phenomenon of the developed world, and that it doesn't exist in the developing world. How could they possibly know what the prevalence rates are in the developing world, if local doctors don't have any training such that they can recognise or identify the illness?

 

[Sidereal]

I'm not too familiar with autism research, and I wonder if aspergers/autism rates are actually rising, or whether perhaps it's just recognition and diagnosis that are improving, along with better statistics gathering?

Years ago, many people with high-functioning aspergers would not have been diagnosed, and many with autism may not have had been recognised as having autism, and may have been given some other label.

Perhaps it's a bit like when some people say that ME/CFS is a phenomenon of the developed world, and that it doesn't exist in the developing world. How could they possibly know what the prevalence rates are in the developing world, if local doctors don't have any training such that they can recognise or identify the illness?

Yep, the better detection/recognition/diagnosis objection has been raised many times in the literature on autism. I don't have any references handy as this is not an area that I'm particularly interested in but as far as I know it has been shown that rates are actually rising and that better recognition of this disorder can only partly account for that.

But yes, as you say, in the past high functioning autism spectrum individuals were not diagnosed with anything. The severely affected ended up with a diagnosis of schizophrenia (when this was a very broad label applied to all kinds of problems, especially by American psychiatrists) or intellectual disability.

 

[barbc56]

@Bob @Sidereal

Bingo! I just read this article which says the same thing.

The recorded prevalence of autism has increased considerably in recent years. This reflects greater recognition, with changes in diagnostic practice associated with more trained diagnosticians; broadening of diagnostic criteria to include a spectrum of disorder; a greater willingness by parents and educationalists to accept the label (in part because of entitlement to services); and better recording systems, among other factors.

This and other studies have also found that the increase in diagnoses occurs mainly among children who are higher functioning, meaning they have more subtle signs of autism, and not very much among lower functioning children with autism. This makes sense in the context of increased surveillance and broadened diagnostic criteria.

My bold.
http://www.sciencebasedmedicine.org/autism-prevalence-unchanged-in-20-years/

Early in my career, I worked with birth to five year old children with developmental delays. Some of these children who would have a diagnosis of autism today would have been labeled as developmentally delayed or retarded. Later when I worked with emotionally disturbed adolescents some of the student's with a label of aspergers would have been labeled with a personality disorder, behavior disorder or emotionally disturbed.

In the same article I have cited, it also discusses that the type of brain changes seen in autism would have to occur in the womb.

Barb

 

[MeSci]

The prevalence of autism spectrum disorders has been rising rapidly in recent decades. Clearly the most important risk factors must be environmental. By environmental I don't mean to imply refrigerator mother or other psychoquackery. I'm talking infections, toxins, diet, antibiotics etc.

The Nature abstract doesn't say what the effect sizes are for these genes (likely abysmal). In general, genetic research has been a total failure in the study of neuropsychiatric disorders and has brought us no closer to better prevention and treatment. An incredible amount of money has been spent on genetic research of this sort. Everyone can judge for themselves if it has led to any therapeutic breakthroughs for autism, schizophrenia, mood disorders, Alzheimer's, Parkinson's, MS, ALS etc.

If there is a genetic component, another reason for increase could be that people are now living long enough to procreate who would previously have died before they could. Example include premature babies surviving due to incubators, etc., and children and adults not catching fatal infectious diseases due to vaccination, or surviving them due to antibiotics and antivirals. Such people might have been 'selected out' by natural selection before. Such people may have a higher likelihood of having children with combinations of SNPs that predispose to autism and/or ME, etc.

 

[natasa778]

There have actually been several studies published in recent years showing that most of the increase in autism numbers is down to actual/real increase. In other words only some of the increase is due to wider criteria/ including milder cases and to diagnositic subsitution but those two factors cannot account for the sharp and steady rise in numbers, not by a long shot.

 

[barbc56]

The study I cited took into accout these other factors. I was surprised by the result as I thought there was a bit of an increase.

This study looks pretty sturdy. There have been other studies showing the same results but they aren't as extensive.

Barb

 

[natasa778]

That study and esp the SBM comment you posted Barb are full of holes, and riddled with (ideological) conflict of interest. All I have time for

 

[chipmunk1]

http://www.theguardian.com/science/...al-scrrening-test-autism-ethical-implications

A large percentage of parents would almost certainly use a prenatal autism test to make a decision on whether to terminate the pregnancy – if the statistics for Down's syndrome since the introduction of prenatal screening are anything to go by. It is believed that around 90% of pregnancies in England and Wales that receive a diagnosis of Down's syndrome are aborted.

Not sure if genetic screening is always a good development.