Increased de Novo Mutations for Older Fathers
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Citation: Whole-genome sequencing of quartet families with autism spectrum disorder
The above is from the supplements of Whole-genome sequencing of quartet families with autism spectrum disorder. You can read about the research in The New York Times. I just wanted to highlight the above scatterplot, especially panel A, in the interests of pro-natalist alarmism about older fathers.
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The plot suggests that the risk for older dads is very slight.
The NY Times story was confusing. It’s example is about a couple with 2 kids, 1 autistic and 1 not. They sought advice on whether the next kid would be autistic. The article says it would be very unlikely, according to the new research. But in fact the next kid was autistic!
The article brags that the authors are putting the data online, but the research article is not even freely available, and behind a $32 paywall.
A few years ago, looking at the available data reported in academic research on autism incidence, and modeling it, parental age (and parental environmental exposure) related new mutations in fathers looked like the dominant source of autism in the absence of a familial history of it, and a very large share of autism cases do not involve a familial history of autism.
The comparative weak correlation in the NYT’s reported study, could simply be a case of missing hereditary components, for example, because multiple genes in combination are necessary to trigger an effect in a way that, for example, dilutes the statistical impact of any particular SNP.
It could also be the case that paternal age does not have the same impact on all genes; autism relevant genes may be more prone to paternal age related mutations than other more stable parts of the genome.
The other key point in that analysis was that there appear to be sex linked protective genes that mitigate autism symptoms in girls much more often than in boys. Autism incidence seems to be due to a combination of affirmatively broken new mutations in a complex subset of genes and the absence of protective genes.
I play with the numbers and recite the data here: http://washparkprophet.blogspot.com/2008/01/new-genetic-model-for-autism.html