Autism and Genetics

Hello Dazzle! Thanks for coming and hanging out with me today, I’m glad that you are here. Today I want to talk about Autism and how science currently understands it’s relationship with genetics. This is a complex topic and because of that, I will be keeping things at a basic level. First, because fully delving into the topic of anything in the realm of genetics is outside the scope of this blog. Secondly, because going into any great depth on the topic is outside my wheel house.

The first thing to touch upon is the fact that what we know about the genetics of autism is complex. There are no clear or perfect answers at this point in time which is why the research is still ongoing. Twin and family studies have provided evidence that autism is largely genetically determined. Yet, there is research that suggests that the twinning process itself is an important risk factor in the development of autism, with major consequences for our interpretation of twin studies. [13] There is also plenty of research that now challenges the diagnostic criteria, if not the diagnosis of autism itself. [15] [25] [27] [31] There is plenty of research to show that many traits associated with autism may in fact be due to alexithymia [45] [46] and that there may be more then one type of autism. [15] [25] [27] [31]

In most cases, it appears that autism is polygenetic [7] or that multiple genetic factors are involved, with each likely contributing only a small amount of risk. There is also good evidence that autism is genetically heterogeneous [1], meaning that there are multiple alleles [5], or possible variations, that can generate the same presenting traits. How these various alleles [5] combine together will impact the over all presentation of traits. Which is a likely factor for the variability in the traits being presented in different individuals. This means that there are numerous possible variations upon the numerous genes that could possibly effect autistic traits. Some of these variations are coding for the same traits as each other while other variations are for different traits or even non-autistic traits.

In addition to that, there are other factors adding to this complexity. There is the influence of epigenetics [8] or the modification of gene expression without changing the DNA. Our body uses DNA methylation (DNAm) [18] [19] to effectively turn on and off our genes. This means that genes can be present in our DNA but not expressed due to being suppressed. There are also de novo mutations [9], which are genetic alterations that present for the first time in one family member as a result of a variant (or mutation) in a germ cell (egg or sperm) of one of the parents. The role of environmental influences on expression is unclear, but is thought to have an impact on the epigenetic level. This is based upon the numerous environmental factors highly correlated with the presentation of autistic traits. [17] [20] All of this makes it very difficult to determine the exact cause of autism.

It is important to understand that while we are discussing our understanding and the current clinical theory regarding the genetics of autism that there has been nothing fully decided upon in the clinical arena. Again, this why the research into the cause of autism is still ongoing. Different experts have different opinions based upon the same research. Thus, it is easy to find literature that presents a multitude of different opinions and thoughts regarding this matter. All of this makes the topic all the more confusing.

Currently, autism is not classified as a genetic disorder. The reason for that is because there is no gene, or set of genes, that when present always produces the traits associated with the autism diagnosis. Additionally, the current research suggests that such a gene or set of genes does not exist for autism. A meta-analysis of seven primary twin studies reported that the heritability estimates ranged from 64% to 93% of the time, rather then the 100% (or very near 100%) that would be expected from a genetic disorder. [17] [21] Additionally, the severity of the various traits is different between the twins. [10] This means that in individuals who have identical DNA, autism does not always present the same way. This implies that there is more impacting the presentation of the autism traits then the person’s DNA.

However, all of that being said, as we learn more about genetics in general we are beginning to realize that there is less black and white about these diseases and that there is much more going on then we previously understood. There are cases where individuals have been found to have the genetic criteria present for a genetic disorder but not meet the clinical diagnostic criteria for that disorder. [47] A large reason that we have always believed that those who had the DNA always had the disorder is because we were only performing the DNA sequencing on those with the presenting symptoms for the disorder. With the rise of genetic testing and increasing available data on individuals without a diagnosis we are beginning to see a different picture. In the end, it may mean that there are far fewer diseases that fall under the label of being genetic disorders rather then having a genetic predisposition.

This does not mean that DNA does not play an important role in autism. What it means is that autism has a genetic predisposition [11] rather then being a genetic disorder. The research clearly demonstrates that there are genes that are commonly present in individuals with autism. This suggests that epigenetics [8] plays a major role in autism. DNA methylation (DNAm) [18] [19], an epigenetic modification, allows for both genetic and environmental factors to modulate a phenotype or observable trait. [2] There is research that demonstrates that DNAm changes are associated with autism. [17] As of yet, there is no indication what activates the DNAm in autistic individuals. However, there are numerous environmental factors (aka not related to DNA) that are correlated with an increased risk for autism: parental age, asphyxia-related birth complications, preterm birth, maternal obesity, gestational diabetes, various medications during pregnancy, [17] and viral infections [20].

Its also important to mention in all of this is that autistic traits [36] are often seen in individuals that do not meet the diagnostic criteria for autism. Genetic relatives of people with autism often show milder expression of traits characteristic for autism, often referred to as the Broader Autism Phenotype (BAP). [16] [25] [35] This suggests that there is a cumulative nature to autism rather then an all or nothing factor. Meaning that a person can have autistic traits and if mild, they can function within society without disfunction, distress or danger. But when those traits become numerous or severe, the individual begins to have difficulties functioning within society; presenting with distress, disfunction or danger.

While many object to autism being included within the DSM5, the preceding information goes a long way to explain why it has found its way included amongst the mental disorders. Like every other disorder within the DSM5, the research for autism suggests that there is a genetic predisposition with significant environmental factors determining the presentation of the disorder. While autism is also classified as a developmental disorder [37] this doesn’t change the fact that it is more similar to the other disorders of the DSM5 then not. There are many that focus upon the idea that they are “born with autism” while those with depression or anxiety develop that later in their lives. Yes, the research suggests that individuals are either born with autism or develop autism while very young. As of yet, we cannot rule out developing autism while an infant or toddler. Yet, what these disorders all have in common is that the disorder is not guaranteed to be present based on the DNA, but rather developed because a person has the DNA and experiences an environmental exposure whether while still in their mother’s womb or during their life.

The other thing that autism has in common with the other disorders within the DSM5 is that the autism traits are found within the family members of those with autism despite not meeting diagnostic criteria. This is also true of the other DSM5 disorders. This is where the idea of being “a little autistic” or “a little ADHD” comes from. This is also why the disorder is considered a spectrum as are the other disorders within the DSM5 despite not being labeled that in the DSM5 itself. [40] [42]

As a final point when discussing autism’s place within the DSM5, there is the undeniable link between Autism Spectrum Disorders and Schizophrenia Spectrum Disorders. Research suggests that 30% of those with autism also present with schizophrenic symptoms, including psychosis. [38] This is much higher then the general population where only about 0.5% of people have schizophrenic symptoms. [39] Efforts have been made to characterize the pattern of cognitive function in both disorders, and similarities have become apparent; such as deficits in abstract reasoning and the more complex aspects of memory and language. [43] However, it is difficult to determine how much of this is due to the historical connections of the two disorders and the interconnected language used to describe them. [44]

Well, that’s about it for my rambling today. Thanks for coming and spending some time with me. If you like what you read, click on that like button. It really does help! Until we talk again, you take care of yourselves!

Additional Reading, Sources and Information

  1. Genetically heterogeneous: A term used to describe different genetic mechanisms that produce the same or similar phenotypes.
  2. Phenotypes: the set of observable characteristics of an individual resulting from the interaction of its genotype with the environment.
  3. Genotype: the genetic makeup of an individual organism.
  4. Genome: the complete set of genes or genetic material present in a cell or organism.
  5. Alleles: one of two or more alternative forms of a gene that arise by mutation and are found at the same place on a chromosome.
  6. Chromosome: a threadlike structure of nucleic acids and protein found in the nucleus of most living cells, carrying genetic information in the form of genes.
  7. Polygenetic: having more than one genetic origin or source.
  8. Epigenetic: the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself.
  9. De novo mutations: A genetic alteration that is present for the first time in one family member as a result of a variant (or mutation) in a germ cell (egg or sperm) of one of the parents.
  10. Castelbaum, L. On the nature of monozygotic twin concordance for autistic trait severity: A quantitative analysis. Behavior Genetics.2019.
  11. Genetic predisposition: An increased chance or likelihood of developing a particular disease based on the presence of one or more genetic variants
  12. Heritability of autism spectrum disorders: a meta-analysis of twin studies
  13. On the Twin Risk in Autism
  14. Genetic correlates of phenotypic heterogeneity in autism
  15. Social and non-social autism symptoms and trait domains are genetically dissociable
  16. Clinical autism subscales have common genetic liabilities that are heritable, pleiotropic, and generalizable to the general population
  17. Genetic contributions to autism spectrum disorder
  18. DNA Methylation and Its Basic Function
  19. DNA methylation regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factor(s) to DNA. Essentially turning portions of the DNA off.
  20. Association between Viral Infections and Risk of Autistic Disorder: An Overview
  21. Association of Genetic and Environmental Factors With Autism in a 5-Country Cohort
  22. “Autism research is in crisis”: A mixed method study of researcher’s constructions of autistic people and autism research
  23. In Prototypical Autism, the Genetic Ability to Learn Language Is Triggered by Structured Information, Not Only by Exposure to Oral Language
  24. Ethical dimensions of translational developmental neuroscience research in autism
  25. A Genetics-First Approach to Dissecting the Heterogeneity of Autism: Phenotypic Comparison of Autism Risk Copy Number Variants
  26. Is there an association between prenatal testosterone and autistic traits in adolescents?
  27. Does the autism phenotype differ when selecting groups by neurodevelopmental versus genetic diagnosis? An observational study comparing autism and sex chromosome trisomy
  28. Mitochondrial dysfunction: A hidden trigger of autism?
  29. Autism spectrum heterogeneity: fact or artifact?
  30. Association of cumulative early medical factors with autism and autistic symptoms in a population-based twin sample
  31. Clinical and translational implications of new understanding of a developmental sub structure for autism
  32. Integrated genetic and methylomic analyses identify shared biology between autism and autistic traits
  33. Association of genes with phenotype in autism spectrum disorder
  34. The contribution of environmental exposure to the etiology of autism spectrum disorder
  35. Autistic Traits Below the Clinical Threshold: Re-examining the Broader Autism Phenotype in the 21st Century
  36. Autistic traits: behavioral patterns characteristic of autism.
  37. Developmental disorder: any condition resulting from atypical or delayed mental or physical development.
  38. Autism Spectrum Disorders and Schizophrenia Spectrum Disorders: Excitation/Inhibition Imbalance and Developmental Trajectories
  39. Schizophrenia
  40. The depressive spectrum: diagnostic classification and course
  41. Depression Spectrum Test
  42. The anxiety disorder spectrum
  43. High-functioning autism and schizophrenia: A comparison of an early and late onset neurodevelopmental disorder
  44. The social ties between autism and schizophrenia
  45. Investigating alexithymia in autism: A systematic review and meta-analysis
  46. Alexithymia and Autism Spectrum Disorder: A Complex Relationship
  47. A case of apparent trisomy 21 without the Down’s syndrome phenotype.

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