Antivaccine nonsense Autism

I wonder how the anti-vaxers and mercury militia will explain this result

It’s been a while since I wrote about autism. Part of the reason is that I’ve been on vacation. Another part of the reason is that not much has been happening lately on the mercury/autism front. I like to think it’s because the evidence has been accumulating so rapidly that neither the MMR vaccine nor mercury-containing vaccines are associated with autism, the claims of the mercury militia notwithstanding, that the last even semireasonable people have started backpedaling, leaving only the hard core, like J. B. Handley. Indeed, I’ve spent a lot of time debunking the claims of the antivaccination crowd and the mercury militia (indeed, so much so that I’ve been described as being “on a mission to discredit any and all evidence of a mercury-autism linkage,” as if that were a bad thing, given the horrible quality of virtually all such evidence that I’ve examined critically over the last year or so and the dubious ethics of key researchers pushing the vaccine-autism link), and this summer there was a new large study that failed to find a link between vaccines (mercury-containing or MMR) and autism.

Right after getting back from vacation, I saw stories about this paper all over the media, whose abstract is here, a study that provides yet more evidence that the etiology of autism is probably primarily genetic, not due to vaccines:

Context: Maternal and paternal ages are associated with neurodevelopmental disorders.

Objective:To examine the relationship between advancing paternal age at birth of offspring and their risk of autism spectrum disorder (ASD).

Design: Historical population-based cohort study.

Setting: Identification of ASD cases from the Israeli draft board medical registry.

Participants: We conducted a study of Jewish persons born in Israel during 6 consecutive years. Virtually all men and about three quarters of women in this cohort underwent draft board assessment at age 17 years. Paternal age at birth was obtained for most of the cohort; maternal age was obtained for a smaller subset. We used the smaller subset (n = 132 271) with data on both paternal and maternal age for the primary analysis and the larger subset (n = 318 506) with data on paternal but not maternal age for sensitivity analyses.

Main: Outcome Measures: Information on persons coded as having International Classification of Diseases, 10th Revision ASD was obtained from the registry. The registry identified 110 cases of ASD (incidence, 8.3 cases per 10 000 persons), mainly autism, in the smaller subset with complete parental age data.

Results: There was a significant monotonic association between advancing paternal age and risk of ASD. Offspring of men 40 years or older were 5.75 times (95% confidence interval, 2.65-12.46; P<.001) more likely to have ASD compared with offspring of men younger than 30 years, after controlling for year of birth, socioeconomic status, and maternal age. Advancing maternal age showed no association with ASD after adjusting for paternal age. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on maternal age. Conclusions: Advanced paternal age was associated with increased risk of ASD. Possible biological mechanisms include de novo mutations associated with advancing age or alterations in genetic imprinting.

This investigators decided to look at maternal and paternal age as risk factors for their children developing autism or autism spectrum disorders (ASDs) because previous studies looking for an association between increasing maternal age and ASDs have been mixed, because of suggestions of an association between increased paternal age and ASDs but no studies had controlled for maternal age. Moreover, there are several studies showing association between paternal age and congenital disorders, an increased risk of schizophrenia, and decreased intellectual capacity. Consequently the authors undertook a study that tried to examine this question and control for ages of both parents. This study was possible in Israel because all Israeli citizens are given a unique identification number at birth or at attaining Israeli citizenship, allowing the linking of parents’ draft board assessments at age 17 and military service files (when present) to those of recent inductees. It is thus possible to calculate the age of both parents of inductees at the time of his or her birth. Furthermore, the draft board assigns ICD-10 diagnoses, and psychiatric diagnoses are assigned by board certified psychiatrists experienced in treating adolescents. Israel also has a system in which virtually all children and adolescents with ASDs are registered with the Israeli Society for Autistic Children (ISAC), and has universal health care. Thus, the assessment and followup is excellent.

Basically, as described above, for the inductees examined during the six years of the study, the investigators found that men over 40 are 5.75 times more likely to produce offspring with an ASD when compared with men under 30. It was a monotonic assocation, meaning that increasing age correlated with increasing risk of producing offspring with ASDs without any glitches or variation, with ASD risk depending on that one variable. In contrast, there was no signficant association between increasing maternal age and ASDs. Multiple control analyses were done, and the effect persisted. Unfortunately, the investigators were not able to determine whether paternal age correlated with specific ASD diagnoses, like autism or Asperger’s disease, because the draft board does not record individualsubtypes of ASDs.

The fascinating thing about this study, if its results hold up, is that it is yet more evidence implicating genetic causes for autism. According to the “copy error” hypothesis, new spontaneous mutations can arise, propagate, and accumulate in successive generations of sperm-producing cells, and this accumulation could produce more and more such abnormalities the older a man is. If these results hold up, they also suggest a potential mechanism that would account for the male preponderance in autism and ASDs. For example, if the genetic abnormalities contributing to autism are linked to the Y chromosome, increasing mutations with age in the father would accumulate in the Y chromosome that he contributes to the offspring. In males, Y-linked genes that contain mutations would not be counteracted by any genes contributed by the mother. However, mutations that might accumulate in the father’s X chromosome would be less likely to have an effect because any mutations in genes of the X chromosome contributed by the father could be countered or ameliorated by the normal copy of the same genes on the X chromosome contributed by the mother. In addition, it suggests one contributing factor that may partially explain the increasing number of diagnoses of ASDs besides changes in administrative prevalence, namely the increasing number of men who are deferring marrying and having children until their 30’s, 40’s, and even 50’s.

In any case, this study is yet another that strongly implicates genetic causes of autism. Given that, I predict that the antivaxers will not like it at all. I predict that they’ll either ignore it or find a way to attack it–or both.

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

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