Genetic Component in Autism Spectrum Disorder

## DSM-V Genetic Factors of ASD

Autism Spectrum Disorder (ASD) heritability estimates range from 37% to >90%, based on twin concordance rates. Approximately 15% of individuals with ASD are associated with a known genetic mutation, with different de novo copy number variants or de novo mutations in certain genes related to the disorder in different families. However, it doesn't seem to be completely penetrant even when autism is linked to a known genetic mutation. The remaining cases seem to be polygenic, with possiblyhundreds of genetic loci creating small contributions.

## Importance of Genetics in ASD

In 1977, Professor Michael Rutter and Dr. Susan Folstein completed the first systematic study of twins with ASD. They showed in their study of 21 British twins that there was a high genetic component in autism. For 10 pairs of fraternal (dizygotic) twins in which at least one of the twins was diagnosed with ASD, none of the single co-twins was diagnosed with ASD: concordance was zero for fraternal twin pairs. Heritable disorders were expected to run in families, which is why the possibility of the influence of genetics for ASD was not researched. For the 11 pairs of identical (monozygotic) twins that were genetically identical, four of the 11 pairs were concordant for an ASD diagnosis. The concordance for cognitive abnormalities was 82% in identical twins and 10% in fraternal twins. The difference in concordance for autism and concordance for cognitive disorder between identical and fraternal twins shows the importance of genetic factors in the etiology of ASD. This was one of the first studies that led to a shift of autism being thought of as an environmentally-caused disorder to being a heritable disorder.

ASD is highly genetically heterogeneous and could be caused by both de novo and inheritable gene variations. Research has shown that the genetic influence on autism is not due to one gene but might be due to many genes of small effect size. Within the past decade, hundreds of genes have been recognized that contribute to the deficits in social cognition, communication, and behavior that individuals with ASD experience. However, these only make up 10-20% of ASD cases. Individuals with similar pathogenic variants might be diagnosed on different levels of the spectrum.

The vulnerability of autism is estimated to be around 40-80% genetic. The remainder of the risk might be comprised of environmental factors most likely acting through epigenetic regulation as the major mechanism. Researchers have identified a variety of potential environmental factors that contribute to an increased risk of ASD such as prenatal exposure to anticonvulsants, maternal complications or infections during pregnancy, and increased parental age.

1. ↑ 1.0 1.1 1.2 1.3 American Psychiatric Association. (2013). *Diagnostic and statistical manual of mental disorders* (5th ed.). Washington, DC. https://doi.org/10.1176/appi.books.9780890425596
2. ↑ 2.0 2.1 2.2 2.3 2.4 Feinstein, A. (2010). *A history of autism: Conversations with the Pioneers*. Wiley-Blackwell.
3. ↑ 3.0 3.1 3.2 3.3 *1977 paper on the First Autism Twin Study*. 1977 paper on the first autism twin study. Retrieved December 6, 2021, from https://web.archive.org/web/20150321221005/http://sfari.org/news-and-opinion/classic-paper-reviews/2008/1977-paper-on-the-first-autism-twin-study-commentary-by-angelica-ronald-and-robert-plomin.
4. ↑ 4.0 4.1 4.2 4.3 4.4 Folstein, S. & Rutter, M. (1977). Infantile autism: A genetic study of 21 twin pairs. *Journal of Child Psychology and Psychiatry, 18,* 297-321.
5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 Rylaarsdam, L., & Guemez-Gamboa, A. (2019, August 20). *Genetic causes and modifiers of autism spectrum disorder*. Frontiers. Retrieved December 6, 2021, from https://www.frontiersin.org/articles/10.3389/fncel.2019.00385/full.