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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22 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

  4. Mike February 18, 2017 at 01:59 #

    IMHO the statement “there can be no genetic epidemics,” is used to discourage the idea that we as humans have evolved maladaptive metabolic programming. Genetic evolution through trait heritability is far too slow to cause a sudden population wide increase in disease. Additionally it would not make sense for evolution to accumulate unfavorable traits that lead to disease.
    I am guessing, that instead of looking at genetics to explain diseases, proponents of this statement would argue that environment and human behavior should be the subject of investigation.
    As you have pointed out discrete mutations and aneuploidy, while genetic in nature, can experience epidemic like increases in incidence, but this is not a result of a heritable progression. Instead it is a result of environmental and behavioral factors such as increased parental age and toxic exposure.

    • Sullivan (Matt Carey) February 19, 2017 at 21:35 #

      Down Syndrome, a genetic condition, has increased significantly in recent decades. Down Syndrome is more prevalent in families with older parents.

      Autism is more prevalent in families with older parents.

      So, yeah, “no genetic epidemics”.

      The main reason, though, why people want to argue “there are no genetic epidemics” is to get people to accept without question that the rise in autism diagnoses reported represents a true increase in the fraction of the population that is autistic.

      Which is a clearly false assumption. Hence the reason they don’t want you to question it.

      • Mike February 21, 2017 at 01:46 #

        Environmental risk factors definitely contribute to the development of autism. Paternal age for instance is one you pointed out.

        The question is: Will we be able to identify more risk factors?

        If additional autisms risk factors do exist, we would be prudent to identify and eliminate them so that we may be able to prevent the disease.

        Pinning the whole case on vaccines or pinning the whole case on increased diagnosis, both are likely incomplete answers. Both are also limiting beliefs. With such little understanding of the pathophysiology of autism, we should not limit possible avenues of research.

        More research and understanding are obviously warranted.

        I for one hope that research will yield results sooner rather than later.

      • Chris February 21, 2017 at 02:25 #

        One known “environmental” risk is Congenital Rubella Syndrome.

    • Lawrence February 21, 2017 at 13:41 #

      Taking a critical look at the available information and evidence –

      1) Over the past 30 – 40 years, both maternal and paternal ages for conceiving children has increased. We also know that advanced age of conception has been linked to an increase (and risk for) a variety of genetic conditions in newborns.

      2) Exposure to diseases like CRS has been to linked to birth defects and mental impairment in newborns – while exposure to disease in general, during pregnancy, is known to lead to stillbirth and spontaneous abortion of the fetus.

      3) In general, toxic exposure in our current environment is actually less today, than it was 50 years ago. Lead exposure, once a ubiquitous occurrence, has dropped dramatically. Overall, sanitation is still much better today than it has been in the past.

      4) Overall, the diagnosis of ID has seen a significant drop, while the rate of diagnosis for the Autism Spectrum increased. This was also part of the expansion of the DSM definition of the autism spectrum, which saw large numbers of children classified as “autistic” while residing on the higher functioning part of the spectrum.

      The overall rate of “highly or severe autism” has remained relatively stable over the course of the DSM changes.

      Now, let’s look at vaccinations over the same time period…

      In general, the overall rate of vaccination in the United States has remained high (90% + on average).

      Despite near uniform vaccination rates across the 50 states, the rate of autism diagnosis varies widely. If vaccination status was at all related to a diagnosis of autism, we would expect to see rates uniform as well – but we don’t.

      For those who would still blame Thimerosal – not only did most vaccines given in the US never contain the preservative, but few, if any pediatric vaccines given over the past 15 years contained it.

      There is also no known biological mechanism by which Thimerosal could cause the symptoms or development of autism.

      For those who blame adjuvants in vaccines – again, the adjuvants used in vaccines has remained stable or the same for a decade or more. When you combine that with 1) no known biological mechanism for causing autism and 2) fairly uniform vaccination rates, the logic of the anti-vax argument falls apart (again).

      And one argument that I put forth as well, includes the fact that when children suffered from the host of childhood diseases (polio, Measles, Mumps, Rubella, Pertussis, etc.) it very likely masked some of the chronic conditions that we see today – including children who might have been autistic, but who then died or were crippled by a bout of disease. Also, the relatively high infant mortality rate also likely masked the diagnosis of autism…along with the very poor conditions and treatments available for those considered “mentally ill or defective.”

      One only needs to read accounts of how the mentally-ill were treated in the past, to realize that many of those committed to asylums or locked away by their families, were probably on the spectrum (as we view it today).

      I find this lack of historical contextual consideration by anti-vaxers, to be yet another reason why they can’t “see the forest for the trees.” I’ve read the “Changling” stories from Medieval Europe – of babies that it was claimed were stolen from their cribs and replaced with “Changling” babies.

      When viewed in context, this certainly sounds a lot like what we see as “regressive autism” today.

      There is also the comparison to Schizophrenia – a condition which manifests itself in the late teens or early twenties of otherwise healthy young people. It is an example of how the development of the brain can “go wrong” for no other reason than a genetic coding error, which flips a switch at a certain time or under certain conditions.

      And lastly, vaccines are supported by international organizations and countries worldwide, many of whom aren’t necessarily friendly or even big fans of international corporations (or capitalism in general). Yet, these same countries embrace vaccinations as a critical piece of protecting their populations from disease.

      It would be easy for a country like Russia or Iran (or North Korea, even) to provide evidence of vaccine harm, if for no other reason than to discredit the United States (and “Big Pharma.”) Yet, this never happens.

      Of course, anti-vaxers will posit an international conspiracy which pays off the millions, upon millions, of people who would be required to be paid to keep the “secret.” Yet, vaccines make up only about 3% of global Pharma sales (about $30 Billion in gross revenue – not profits, just revenue).

      Just doing the math, alone, shows how ridiculous the argument is.

      Sorry for the long post, but I thought it was worthwhile to get my thoughts down. Thanks.

      • Mike February 23, 2017 at 01:20 #

        Thank you for the thorough reply. I just want to add that I know vaccinations have 100% been beneficial for mankind. I think my only point was that some people who become so staunchly against anti vaccers, close their minds to the potential of a preventable risk factor of autism. It sounds like you have made a good effort in researching many variables, whether risks or otherwise. I commend you for that. Some day, we will discover the biological mechanism and get to the root of this all

      • Sullivan (Matt Carey) February 23, 2017 at 18:03 #

        People who have spent a great deal of time reading and understanding the research on vaccines and autism have not “close[d] their minds to the potential of a preventable risk factor of autism”.

        On the contrary, they have shown a great open mindedness that is lacking in most of those who promote the idea that vaccines cause autism.

        Countering misinformation spread by people who promote the idea that vaccines cause autism is not being “staunch[ly] against anti vaccers”. It is understanding the facts and the damage that those who promote untruths are causing.

      • Mike February 24, 2017 at 14:46 #

        I agree, those who spend a great deal of time reading and understanding the research, or conducting research themselves are not the ones closing their minds. I just finished commending Mr. Lawrence on his own well rounded understanding.

        In my previous posts I was only pointing out that there is a sentiment among some lay people that the sole source of increases in autism incidence is increased diagnosis.

        As a lay person myself, in the area of autism research, my sentiment is that the potential for discovery in the research of autism is exciting. For example, I have read a few articles regarding the comorbidity of autism and GI ailments. Gut inflammation and GI biomes, and their interactions with systemic inflammation and neural circuitry is just one of probably many promising areas of research in autism. Although it may not be a cure it seems like a promising avenue for symptom alleviation.

      • Lawrence February 23, 2017 at 15:50 #

        Thanks Mike. I merely wanted to point out that there were many other, more likely areas of research & that continuing to spend time and attention on vaccines (trying to connect them to autism) was a huge waste of time and resources.

      • Lawrence February 24, 2017 at 15:11 #

        @Mike – you bring up another excellent point. There are a number of conditions that appear to afflict those with autism, in percentages greater than the general population.

        It is well known that genetic conditions, like Downs Syndrome, for instance, also present with other, physical defects, like heart valve irregularities and other physical deformities and organ problems.

        This leads us back to autism being a condition that is primarily genetic in nature, but which can present in a variety of different, though similar across the spectrum, ways.

        Making these types of comparisons and examining all of the available medical research evidence, allows us to gain greater insight into autism as not only a mental condition, but that some physical traits may manifest as well.

        These are all areas of research which deserve attention.

      • Chris February 24, 2017 at 21:08 #

        Mike: “As a lay person myself, in the area of autism research, my sentiment is that the potential for discovery in the research of autism is exciting.”

        Indeed, there is a great deal of research that has discovered actual genetic sequences that show common symptoms of autism like similar facial features and even GI issues (like this de novo mutation). There are now some parent groups of children with specific genetic differences (there was a slide at autism genetics presentation I went too, but I forgot to write down the numbers, sorry).

        Anyway, one reason for the presentation was to recruit more families in a nation wide family genetics study:
        https://sparkforautism.org/

        It involves a consent form, questionnaire and swab kits that at a minimum one for each parent and their child on the spectrum.

      • Chris February 24, 2017 at 21:09 #

        Failed the HTML for the embedded link on the de novo mutation link:
        https://spectrumnews.org/news/cluster-of-symptoms-reveals-genes-link-to-autism-subtype/

      • Mitch May 1, 2017 at 17:10 #

        Wow. The ignorance on vaccines is real! Why don’t you do some research on Gardasil and the countries in which it has been BANNED due to injuries (1 out of 10 girls get a severe injury from the vaccine). How about the DPT shot? It wasn’t banned anywhere?

      • Sullivan (Matt Carey) June 20, 2017 at 19:57 #

        Yes. The ignorance on vaccines is real. I’d love to help you get past that but I don’t have the time

  5. Roger Kulp March 1, 2017 at 03:09 #

    If anything we are finding that once we get past the
    more obvious cases,like Fragile X,and even Rett Syndrome,most genetically based autism,is due to “rare” genetic disorders.Often de novo mutations.No tool has been as effective as whole exome sequencing in finding such disoders,as I know all too well.Here is a partial list of such disorders. http://www.pedneur.com/article/S0887-8994(16)30572-0/fulltext?rss=yes

    As impressive as this may list be,it only represents one lab that does WES testing on people with autism.

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