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Cite: Sandin, Sven, et al. “The familial risk of autism.” JAMA 311.17 (2014): 1770-1777.

My wife and I are hoping to have more children. I am pretty convinced of paternal age effect,* so aside from issues like Down Syndrome, which is due to maternal age, the risk for various behavioral issues such as autism are on the radar for us. Also, there are people in the extended pedigree who are probably on the Asperger spectrum (I probably would characterize myself as on the spectrum, but many people who have met me contend that this just isn’t a good description and so might confuse or mislead readers who only know me from the blog. It might be more accurate to say that I’m low on “agreeability”). But should I be worried?

This weekend I heard about a documentary, Mimi and Donna, which is about a 90 year old woman who has to confront letting her 60 year old daughter be institutionalized. Because of her age the woman has never been properly diagnosed, but she definitely has some sort of “intellectual disability.” Today she might have been diagnosed with autism. The film-maker is the grand-daughter of Mimi, and the niece of Donna. What she said was very interesting to me. Her brother has a son with autism, and she herself has a son with autism. As she admits, it runs in the family. Though as I stated above some of my family members exhibit behavior which might seem on the Aspergers end of the spectrum (and I do have a lot of physical scientists and engineers in my pedigree), none of them have been diagnosed autism, nor are they mentally retarded in any way.

As of now my daughter is nearly 3 years old and displays no sign of autism, and my son is young yet but makes eye contact and is socially typical (yes, I am aware of later onset). So I began to realize perhaps I should at least update my odds a bit. I may contribute de novo mutations for risk, but it seems that I don’t carry them from previous generations. I found a large Swedish study, The Familial Risk of Autism, which outlines clearly the odds conditional on affected or unaffected siblings. The figure above is from that paper, and here are the results:

Results In the sample, 14 516 children were diagnosed with ASD [Autism spectrum disorder], of whom 5689 had autistic disorder. The RRR [relative recurrence risk] and rate per 100 000 person-years for ASD among monozygotic twins was estimated to be 153.0 (95% CI, 56.7-412.8; rate, 6274 for exposed vs 27 for unexposed ); for dizygotic twins, 8.2 (95% CI, 3.7-18.1; rate, 805 for exposed vs 55 for unexposed); for full siblings, 10.3 (95% CI, 9.4-11.3; rate, 829 for exposed vs 49 for unexposed); for maternal half siblings, 3.3 (95% CI, 2.6-4.2; rate, 492 for exposed vs 94 for unexposed); for paternal half siblings, 2.9 (95% CI, 2.2-3.7; rate, 371 for exposed vs 85 for unexposed); and for cousins, 2.0 (95% CI, 1.8-2.2; rate, 155 for exposed vs 49 for unexposed). The RRR pattern was similar for autistic disorder but of slightly higher magnitude.We found support for a disease etiology including only additive genetic and nonshared environmental effects. The ASD heritability was estimated to be 0.50 (95% CI, 0.45-0.56) and the autistic disorder heritability was estimated to 0.54 (95% CI, 0.44-0.64).

I am aware that the basal risk is low. But the cumulative sum of a lot of independent low risks can be quite stressful.

* A presentation at ASHG 2014 which had huge sample sizes (~1000 trios) with whole genome sequencing convinced me that paternal age effect shouldn’t be doubted. It’s real.

• Category: Science • Tags: Behavior Genetcs 
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Father_and_son_27Update: This is a piece from last June, so not actually timely. Rather, it was being passed around on Twitter recently. So I’m wrong in some details of when the piece as published, but I think my point about the “take home” of Wilcox’s profile as a public intellectual still holds water.

Totally on cue after my last post The Atlantic has a piece out from the omnipresent W. Bradford Wilcox, The Distinct, Positive Impact of a Good Dad. The portions of the article outlining the descriptions of how fathers interact differently with their offspring are totally unpersuasive to me for the reasons I’ve outlined earlier: I believe on average many long term life outcomes which are due to cultural influences are from one’s milieu, one’s “village” so to speak, not one’s parents. The more interesting and superficially persuasive element of Wilcox’s argument has to do with correlations. In particular:

The story told by this data, then, suggests that there is a case to make against the fathers who fail to have good-enough relationships with their children. At least on these outcomes, single mothers do about as well for their children, compared to dads who have poor-quality relationships with their children. By contrast, great, and even good-enough dads, appear to make a real difference in their children’s lives.

I accept the correlations. But I think Wilcox’s case is totally gene-blind.* To illustrate the problem, imagine that you saw a correlation between fathers and sons in terms of empathy. One hypothesis might be that children learn how to engage with others from seeing how their parents engage with others. But another model would take into account genetic dispositions in personality.** When Wilcox reports that individuals who had a bad relationship with their parents have worse life outcomes he neglects to consider that these parent-offspring pairs may share a heritable disposition toward disagreeability.

When I say fathers don’t matter that much, I mean that some of the correlation that you see in these sorts of comparisons are almost certainly due to heritable dispositions which lead to a wide range of life outcomes. For example, having a quick temper and being unable to suppress your emotional responses are going to cause problems within your family and probably diminish chances for success in the workplace. If this tendency is heritable in any way you’re naturally going to see a correlation between families with violence and strife, and offspring who have lower career success and familial stability than their intelligence or education might predict. Of course it is likely that fathers matter in substantive ways. The problem is simply to attribute all of the effect seen in these studies to the environmental shaping of paternal behavior. Sperm matters.

* More precisely, he’s heritability-blind, but you get the picture.

** For readers who are not clear on this, I believe cultural norms are probably the biggest variable which explains many personality traits. Though variation within cultures is still going to be substantially heritable.

• Category: Science • Tags: Behavior Genetcs 
Razib Khan
About Razib Khan

"I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. If you want to know more, see the links at"