There can’t be a genetic epidemic?

20 Nov

It’s a phrase that is heard a great deal in online discussions about autism: there are no genetic epidemics. Genes don’t change quickly enough for a genetic condition to see an increased prevalence over a single generation, right? Well, yes and no.

Consider Down Syndrome. A condition almost everyone would agree is genetic. Per the NIH website: Down syndrome is a genetic condition in which a person has 47 chromosomes instead of the usual 46. Most Down Syndrome children are born to non-Down Syndrome parents. I.e. the genetic condition is not inherited. DS risk increases significantly with the age of the mother. Here is a graph showing estimated DS risk as a function of maternal age (source):

Down Syndrome genetic testing is well established, allowing for prenatal testing and parental choice to terminate pregnancies. An estimated 2/3 of Down Syndrome pregnancies are terminated.

Thus there are at least two social factors which impact Down Syndrome incidence: maternal age and parental choice. Average maternal age is going up, and there are indications that termination rates are going down. These social factors and possibly other factors have led to–a genetic epidemic. Down Syndrome prevalence has been steadily climbing for years:

Per the article in Pediatrics, Prevalence of Down Syndrome Among Children and Adolescents in 10 Regions of the United States:

From 1979 through 2003, the prevalence of DS at birth increased by 31.1%, from 9.0 to 11.8 per 10000 live births in 10 US regions. In 2002, the prevalence among children and adolescents (0–19 years old) was 10.3 per 10000. The prevalence of DS among children in a given age group consistently increased over time but decreased with age within a given birth cohort. The pooled prevalence of DS among children and adolescents was lower among non-Hispanic black individuals and other racial/ethnic groups compared with non-Hispanic white individuals; it was also lower among females than males.

What does this mean for autism? At present there is no commonly used test for autism, but there are strong indications that parental age (both maternal and paternal) increase autism risk. Peter Bearman at Columbia calculated that about 11% of the increase in the administrative autism prevalence in California was due to increased parental age. Groups that promote autism as vaccine injury have been antagonistic towards the idea that parental age, especially paternal age, increases autism risk. The reasons are fairly obvious: they indicate that the idea of “there can be no genetic epidemic” is, at best, a much more complicated statement than they would have us believe.


By Matt Carey

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6 Responses to “There can’t be a genetic epidemic?”

  1. krissy November 20, 2012 at 23:26 #

    Eugenics is terrible… “why do they hate us?”

  2. TLPG November 23, 2012 at 06:27 #

    Matt, I do take a little bit of offence to the comparison between Autism and Downs in the use of the term “epidemic” – because Downs does have a permanent down side. A short life that no one can do anything about. (IIRC) Autism on the other hand doesn’t have such a restriction within itself. Just making that brief point while I work on a new blog against MJ over on Jabberwocky (he’s done a reply to this that I am taking apart).

    • Sullivan (Matt Carey) November 23, 2012 at 15:50 #

      TLPG,

      First, I’m not making much more of a comparison than autism and Down Syndrome (DS) are developmental disabilities and, for a sizable fraction, autism has genetic roots.

      Are you referring to the fact that life span for people with DS is about age 55?

      http://www.nads.org/pages_new/facts.html

      I see many points in which Down syndrome is relevant to the autism discussion.

      First, it wasn’t that long ago that life expectancy for someone with DS was much shorter. Through understanding the medical issues involved life expectancy has been increased.

      All too often I read people say that genetic conditions can not be treated, but autism as “vaccine injury” can. Genetic conditions *can* be treated and there’s no logic behind the alt-med methods and vaccine injury.

      Also, this goes to the discussion if cure vs. treatment. Neither autism nor DS has a cure in place or in trials. But one can still offer treatments which improve quality of life.

      Another thing about DS is that it is genetic but not in the dominant/regressive gene type. Almost all DS children are born to non DS parents. They don’t carry a “DS” risk gene. Much of autism genetics is de novo. I often read “no one in my family is autistic, this can’t be genetic in our case”, which is false.

      The idea of parental age, especially paternal age, has been rejected out of hand by those promoting autism as vaccine injury. It’s not hard to see why.

    • Sullivan (Matt Carey) November 23, 2012 at 16:00 #

      Also,

      I apologize for any offense. I do see your point.

      One thing I would say is at this point we don’t know what autism is like in older individuals. We know it isntr as dramatic as DS in terms of short life expectancy, but little else. Are there early-onset conditions in some fraction of the population? In DS early-onset dementia is common. Is there something that we should know about autism and old age? More simply, how does normal dementia and autism present? How do we serve thast population? Do we have to wait 40 years to find out as this generation of children ages?

      This is one of the failings of those who have promoted the idea that autism is “new”. We are left unprepared.

      • TLPG November 24, 2012 at 14:19 #

        I agree with your last sentence, and there is an explanation for that in my opinion. In the early days (I’m speaking prior to Kanner) anyone who was “not normal” was thrown into asylums – and treated like absolute crap. Under those circumstances a short life was inevitable – and unlike Downs it was not the fault of Autism itself. I firmly believe that Autism and Emil Kraepelin’s “Youth Dementia” were the same thing just to back that view up.

        I did read a story (and I wish I could link it) that introduced us to one of Kanner’s patients – still alive in his 70’s and playing golf (a special interest presumably). As much as he is such a fool, Jonathan Mitchell is aging now, and actually I’m not that far behind him (he’s in his 50’s and I’m approaching 50). As we are polar opposites on the level of self esteem, it will be interesting to see how much longer Mitchell carries on – as well as myself of course. I don’t know how old Temple Grandin is now, but she would be one to watch also.

        Just to finish, I consider 55 still to be too young. That compares to the maximum life expectancy (as distinct from average) of an African living outside the cities of the continent, and maybe the average for the Australian Aborigines. That fact is worrying the government here as it should. The same should be said for Downs.

  3. RA Jensen November 24, 2012 at 12:01 #

    Can a genetic epidemic exist? The answer is, at least in part, is yes. Klinefelter Syndrome (KS) was first identified in1942. KS is associated with risk for intellectual disability, speech and language impairments, autism, breast cancer, auto-immune disease, low testosterone production and social impairments. KS is now the most common genetic syndrome affecting only males in 1 in 500 – 1,000 newborns. KS is not inherited and is always caused by an extra X chromosome. Half the cases are caused by an XY sperm mutation and half are caused by an XX egg mutation producing the KS genotype of XXY.

    http://genetics.emedtv.com/klinefelter-syndrome/history-of-klinefelter-syndrome.html

    http://ghr.nlm.nih.gov/condition/klinefelter-syndrome

    http://pediatrics.aappublications.org/content/129/4/769.abstract

    McAuliffe’s group recently (2011) examined the sperm in males recruited from a fertility clinic and found that all the sub-fertile males had produced XY sperm. They then examined the level of exposure to PCB and DDT congeners measured in blood. Increased level of exposure to PCB and DDT congeners was associated with increased production of XY sperm. PCB and DDT were banned in the US in the 1970’s. These environmental toxins contain multiple component parts and what was thought to be the most offensive component parts were banned but multiple component parts of PCB’s and DDT (congeners) are still used in the more advanced classes of pesticides. PCB and DDT congeners have a long-lasting half-life and can build up over time. Lowe examined the sperm in fathers of KS boys and found that increased production of XY sperm was associated with increasing paternal age. None of the fathers possessed the XXY mutation, the mutations were found only in reproductive cells (sperm).

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1274351/

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339457/pdf/ehp.1104017.pdf

    Benzene is a common constituent in all fossil fuels, petroleum, natural gas and coal. The burning of fossil fuels release Benzene particles into the atmosphere. Benzene is also used as an additive in the production of refined gasoline. The Chinese Benzene and Sperm Study (C-BASS) group is a collaboration between US NIH and Chinese environmental scientists. A year ago they recruited 30 workers in manufacturing plants in China who were heavily exposed to Benzene as part of the manufacturing process and divided the workers into three groups, a low exposure group, a moderate exposure group and a high exposure group. A control group of unexposed workers were also recruited. Sperm mutations were found in all groups and the frequency of sperm mutations increased with higher levels of exposure. 1p36 sperm mutations were found in all groups. 1p36 deletion syndrome is one of the most devastating genetic syndromes.

    http://ghr.nlm.nih.gov/condition=1p36-deletion-syndrome

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279447/

    How common are sperm mutations in the general male population? Molina et al (2011) examined the sperm of 10 healthy male sperm donors. Every male produced sperm mutations that causes 7q11.23 (Williams Syndrome), 15q11q13 (Angelman Syndrome) and 22q11.2 (DiGeorge Syndrome). What this study implicates is that all males, and by inference all females, are at risk for producing a child with a devastating genetic syndrome. The genetic syndromes that are at high risk for autism that are caused by a reproductive error (egg or sperm) include Downs’s syndrome, Klinefelter syndrome, Angelman syndrome, Prader-Willi syndrome. Williams’s syndrome, Rhett syndrome, 22q11 deletion syndrome, 1p36 deletion syndrome as well as other rarer genetic syndromes. Almost all cases are not inherited.

    http://www.ncbi.nlm.nih.gov/pubmed/20931230

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