User:Jules2992/Heritability of autism

Heritability of autism

The heritability of autism is the proportion of differences in expression of autism that can be explained by genetic variation; variation of gene expression in autism. If the heritability of a condition is high, then the condition is considered to be primarily genetic. Although autism has a strong genetic basis, the genetics of autism are complex. and it is This makes it unclear whether autism spectrum disorder (ASD) is explained more by multigene interactions or by rare mutations with major effects.

This is a representation of what a mutation looks like in a autism-related gene.

Early studies of twins twin studies estimated the heritability of autism to be more than 90%. In other words, that 90% of the differences between autistic and non-autistic individuals are due to genetic effects. This, however, may be an overestimate. New twin data and models with structural genetic variation are needed. When only one identical twin is autistic, the other often has learning or social disabilities. For adult siblings, the likelihood of having one or more features of the broader autism phenotype might be as high as 30%, much higher than the likelihood in controls.

Genetic linkage analysis has been inconclusive; many association analyses have had inadequate power. For each autistic individual, mutations in more than one gene may be implicated. Mutations in different sets of genes may be involved in different autistic individuals. There may be significant interactions among mutations in several genes, or between the environment and mutated genes. By identifying genetic markers inherited with autism in family studies, numerous candidate genes have been located, most of which encode proteins involved in neural development and function. However, for most of the candidate genes, the actual mutations that increase the likelihood for autism have not been identified. Typically, autism cannot be traced to a Mendelian (single-gene) mutation or to single chromosome abnormalities such as fragile X syndrome or 22q13 deletion syndrome.

The large number of autistic individuals with unaffected family members may result from copy number variations (CNVs)—spontaneous alterations in the genetic material during meiosis that delete or duplicate genetic material. Sporadic (non-inherited) cases have been examined to identify candidate genetic loci involved in autism. A substantial fraction of autism may be highly heritable but not inherited: that is, the mutation that causes the autism is not present in the parental genome.

Although the fraction of autism traceable to a genetic cause may grow to 30–40% as the resolution of array CGH improves, several results in this area have been described as incautiously. This possibly misleads the public into thinking that a large proportion of autism is caused by CNVs and is detectable via array CGH, or that detecting CNVs is tantamount to a genetic diagnosis. The Autism Genome Project database contains genetic linkage and CNV data that connect autism to genetic loci and suggest that every human chromosome may be involved. It may be that using autism-related subphenotypes instead of the diagnosis of autism per se may be more useful in identifying susceptible loci.

Background

The heritability of autism, a neurodevelopmental disorder characterized by impaired social interaction and communication, has been an area of significant research and debate. Autism is known to have a strong genetic component, with studies consistently demonstrating a higher prevalence of autism among siblings and in families with a history of the disorder. This has led researchers to investigate the extent to which genetics contribute to the development of autism. Numerous studies, including twin studies and family studies, have estimated the heritability of autism to be around 50-80%, indicating that genetic factors play a substantial role in its etiology. However, it is important to note that heritability estimates do not imply that autism is solely determined by genetics, as environmental factors and gene-environment interactions also contribute to the development of the disorder. Understanding the heritability of autism is crucial for advancing our knowledge of its underlying mechanisms and for informing genetic counseling and early intervention strategies.

Twin Studies

Twin studies provide a unique opportunity to explore the genetic and environmental influences on autism spectrum disorder (ASD). Identical twins, who share nearly identical DNA, offer a compelling case when one twin is diagnosed with autism while the other is not. Twin studies are a helpful tool in determining the heritability of disorders and human traits in general. They involve determining concordance of characteristics between identical (monozygotic or MZ) twins and between fraternal (dizygotic or DZ) twins. Possible problems of twin studies are: (1) errors in diagnosis of monozygosity, and (2) the assumption that social environment sharing by DZ twins is equivalent to that of MZ twins. These studies have consistently demonstrated that genetics play a significant role in the development of autism, with heritability estimates ranging from 60% to 90%. By comparing the rates of autism among identical twins (who share 100% of their genes) and fraternal twins (who share around 50% of their genes), scientists can distinguish between genetic and environmental factors. The findings have suggested that genetic factors contribute substantially to autism susceptibility. However, the role of environmental factors cannot be overlooked. Twin studies have shed light on the interplay between genetics and the environment, emphasizing the importance of both in understanding the origins of autism. Through these investigations, scientists hope to pave the way for earlier diagnosis, improved interventions, and ultimately, a better quality of life for individuals on the autism spectrum.

A condition that is environmentally caused without genetic involvement would yield a concordance for MZ twins equal to the concordance found for DZ twins. In contrast, a condition that is completely genetic in origin would theoretically yield a concordance of 100% for MZ pairs and usually much less for DZ pairs; depending on factors such as the number of genes involved and assortative mating.

An example of a condition that appears to have very little if any genetic influence is irritable bowel syndrome (IBS), with a concordance of 28% vs. 27% for MZ and DZ pairs respectively. An example of a human characteristics that is extremely heritable is eye color, with a concordance of 98% for MZ pairs and 7–49% for DZ pairs depending on age.

Identical twin studies put autism's heritability in a range between 36% and 95.7%, with concordance for a broader phenotype usually found at the higher end of the range. Autism concordance in siblings and fraternal twins is anywhere between 0 and 23.5%. This is more likely 2–4% for classic autism and 10–20% for a broader spectrum. Assuming a general-population prevalence of 0.1%, the risk of classic autism in siblings is 20- to 40-fold that of the general population.

Notable twin studies have attempted to shed light on the heritability of autism.

A small scale study in 1977 was the first of its kind to look into the heritability of autism. It involved 10 DZ twins and 11 MZ twins in which at least one twin in each pair showed infantile autism. It found a concordance of 36% in MZ twins compared to 0% for DZ twins. Concordance of "cognitive abnormalities" was 82% in MZ pairs and 10% for DZ pairs. In 12 of the 17 pairs discordant for autism, a biological hazard was believed to be associated with the condition.

Sibling studies

Sibling studies have played a crucial role in understanding the heritability of autism spectrum disorder (ASD). These studies involve examining the occurrence of ASD in siblings of individuals with autism. Research has consistently shown that siblings of individuals with autism are at a higher risk of developing the disorder compared to the general population. According to a study published in the Journal of the American Medical Association (JAMA), the recurrence risk for autism in full siblings is estimated to be around 18.7%, much higher than the prevalence rate in the general population. Another study published in the journal JAMA Psychiatry found that the risk of autism in siblings increases significantly with the number of affected older siblings. These findings strongly support the role of genetic factors in the development of autism. Additionally, a meta-analysis published in the journal Molecular Psychiatry demonstrated that shared genetic factors account for approximately 50-70% of the risk for ASD, further emphasizing the importance of sibling studies in establishing the heritability of autism. These studies have provided valuable insights into the complex interplay between genetics and autism, shedding light on the genetic basis of the disorder and contributing to our understanding of its etiology.

A study of 99 autistic probands which found a 2.9% concordance for autism in siblings, and between 12.4% and 20.4% concordance for a "lesser variant" of autism.

A study of 31 siblings of autistic children, 32 siblings of children with developmental delay, and 32 controls. It found that the siblings of autistic children, as a group, "showed superior spatial and verbal span, but a greater than expected number performed poorly on the set-shifting, planning, and verbal fluency tasks."

A 2005 Danish study looked at "data from the Danish Psychiatric Central Register and the Danish Civil Registration System to study some risk factors of autism, including place of birth, parental place of birth, parental age, family history of psychiatric disorders, and paternal identity." It found an overall prevalence rate of roughly 0.08%. Prevalence of autism in siblings of autistic children was found to be 1.76%. Prevalence of autism among siblings of children with Asperger syndrome or PDD was found to be 1.04%. The risk was twice as high if the mother had been diagnosed with a psychiatric disorder. The study also found that "the risk of autism was associated with increasing degree of urbanisation of the child's place of birth and with increasing paternal, but not maternal, age."

A study in 2007 looked at a database containing pedigrees of 86 families with two or more autistic children and found that 42 of the third-born male children showed autistic symptoms, suggesting that parents had a 50% chance of passing on a mutation to their offspring. The mathematical models suggest that about 50% of autistic cases are caused by spontaneous mutations. The simplest model was to divide parents into two risk classes depending on whether the parent carries a pre-existing mutation that causes autism; it suggested that about a quarter of autistic children have inherited a copy number variation from their parents.

Neurodiversity vs. Autism

On a genetic scale, neurodivergent conditions and autism share some similarities and differences. Several studies have identified common genetic variations that may contribute to both neurodivergent conditions and autism spectrum disorder (ASD). For instance, research published in the journal Neuron indicates that certain genetic mutations, such as those affecting synaptic genes and neuronal communication pathways, are found in individuals with various neurodevelopmental conditions, including autism. Additionally, a study published in Nature Genetics reported that some genetic variants associated with neurodivergent conditions, like schizophrenia and intellectual disabilities, overlap with those implicated in autism. These shared genetic factors suggest potential underlying mechanisms linking these conditions.

However, it is important to note that neurodivergent conditions and autism also exhibit distinct genetic features. A comprehensive analysis published in JAMA Psychiatry highlighted that while there may be shared genetic risk factors across neurodevelopmental conditions, there are also unique genetic variants specific to each disorder. For instance, some genes associated with language development and social cognition are specifically linked to autism. Moreover, a study published in the journal Molecular Autism found that certain genetic pathways are more strongly associated with autism than with other neurodivergent conditions, underscoring the condition's genetic specificity.

Personal Opinion (not going to include in article)

This article is very interesting to me. I am very interested in the link that has been made between autism and genetics. The author seems to have a more bias tone, due to the fact that they tend to repeat themselves often. There are also not any sources on this article past the year 2010. This brings into question the credibility and reliability of this research. Personally, I do believe that there is a link between genetics and autism, but more recent research supporting the claim would help the cause. I also noticed many run on sentences. The author used commas to break up sentences where there should have been a sentence break with a period or at least a semicolon. For example, this sentence "Although the fraction of autism traceable to a genetic cause may grow to 30–40% as the resolution of array CGH improves, several results in this area have been described incautiously, possibly misleading the public into thinking that a large proportion of autism is caused by CNVs and is detectable via array CGH, or that detecting CNVs is tantamount to a genetic diagnosis," has a lot going on and needs to be broken up. Honestly, it is hard to read and clearly understand. The author does keep a amore neutral tone, but with no recent research it seems like they were choosing articles that fit to their claim. The article "Advances in autism genetics: on the threshold of a new neurobiology" is a active cite with reliable research. The study was very interesting. Under the "other families studies" section I was surprised that the researcher used parents with a child diagnosed with down syndrome as a control. The research proved that parents with children with autism were more "more aloof, untactful and unresponsive," but it doesn't clearly state why that is. Some children with autism don't like interaction and prefer to be left alone. So, my question would be if it is the parents choice or just happens subconsciously.

Bibliography

Abrahams BS, Geschwind DH (May 2008). "Advances in autism genetics: on the threshold of a new neurobiology". Nature Reviews. Genetics. 9 (5): 341–55. doi:10.1038/nrg2346. PMC 2756414. PMID 18414403.

Abrahams, B. S., Arking, D. E., Campbell, D. B., Mefford, H. C., Morrow, E. M., Weiss, L. A., Menashe, I., Wadkins, T., Banerjee-Basu, S., & Packer, A. (2013). SFARI gene 2.0: A community-driven knowledgebase for the autism spectrum disorders (ASDs). Molecular Autism, 4, 36

https://link.springer.com/content/pdf/10.1186/2040-2392-4-36.pdf

Hargan-Calvopina, J., Taylor, S., Cook, H., Hu, Z., Lee, S. A., Yen, M. R., Chiang, Y.-S., Chen, P.-Y., & Clark, A. T. (2016). Stage-specific demethylation in primordial germ cells safeguards against precocious differentiation. Developmental Cell, 39(1), 75– 86. https://www.sciencedirect.com/science/article/pii/S1534580716305123?pes=vor

https://www.sciencedirect.com/science/article/abs/pii/S0006899310023449

Krishnan, A., Zhang, R., Yao, V., Theesfeld, C. L., Wong, A. K., Tadych, A., Volfovsky, N., Packer, A., Lash, A., & Troyanskaya, O. G. (2016). Genome-wide prediction and functional characterization of the genetic basis of autism spectrum disorder. Nature Neuroscience, 19(11), 1454– 1462. https://doi.org/10.1038/nn.4353 https://www.nature.com/articles/nn.4353

Peer review edits

Positive not popular pysch: Thank you so much for offering such helpful advice. I am definitely working towards finding more up to date sources. I really appreciate the link you sent me from the O'Neal library. That is a great resource and I completely forgot to check it out!

Filmfanatic88: Thank you for taking to time out of your day to read and review my work. You were correct when you stated that I have not added my "unique contribution" yet. I am still working on reading all of my sources to figure out which way I want to go with it. I will be removing some of the "problematic sources," I just want to be sure that they are not useful before I completely delete them.

Jkb0001: Thank you for your opinions! I agree with you that the "Twinning Risk" section doesn't really make any sense and it distracting. I was on the fence about having it removed, but now I will do that. I am also working to find more up to date sources.

AvonnaPollard22: Thank you so much for all of your recommendation. I will definitely be making this way more organized and easier to follow. I noticed there are many run on sentences and I am working toward finding them all and editing them. Above I state that I am thinking about removing the "Twinning Risk" section, but I may just move it around and add to it. Maybe change the name so people don't get confused.

PsychgirlTYTY: Thank you for your kind words, although I disagree. I know the article can improve a lot and any criticism is welcome! I am working to shorten some of the sections and bring more clarity into the article. I am also looking for more recent sources to strengthen the article.