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Heritability of autism

The heritability of autism is the proportion of differences in expression of autism that can be explained by genetic variation; if the heritability of a condition is high, then the condition is considered to be primarily genetic. Autism has a strong genetic basis. Although the genetics of autism are complex, autism spectrum disorder (ASD) is explained more by multigene effects than by rare mutations with large effects.[1][2]

Autism is known to have a strong genetic component, with studies consistently demonstrating a higher prevalence among siblings and in families with a history of autism. This 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 80 to 90%,[3] indicating that genetic factors play a substantial role in its etiology. Heritability estimates do not imply that autism is solely determined by genetics, as environmental factors also contribute to the development of the disorder.[4]

Studies of twins from 1977 to 1995 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.[5] When only one identical twin is autistic, the other often has learning or social disabilities.[6] For adult siblings, the likelihood of having one or more features of the broad autism phenotype might be as high as 30%,[7] much higher than the likelihood in controls.[8]

A variety of genetic associations with autism spectrum disorder have been reported. These associations are much more common than rare mutations, and each individual variant has a relatively small effect.

Though genetic linkage analysis have been inconclusive,[9] many association analyses have discovered genetic variants associated with autism.[10] For each autistic individual, mutations in many genes are typically 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.[11][12] 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.[13][14]

10–15% of autism cases may result from single gene disorders or copy number variations (CNVs)—spontaneous alterations in the genetic material during meiosis that delete or duplicate genetic material.[15][16][17] These sometimes result in syndromic autism, as opposed to the more common idiopathic autism.[18][19] 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.[20]

Although the fraction of autism traceable to a genetic cause may grow to 30–40% as the resolution of array comparative genomic hybridization (CGH) improves,[20] 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.[21] 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.[22] It may be that using autism-related sub-phenotypes instead of the diagnosis of autism per se may be more useful in identifying susceptible loci.[23]

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  2. ^ Weiner DJ, Wigdor EM, Ripke S, Walters RK, Kosmicki JA, Grove J, et al. (July 2017). "Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders". Nature Genetics. 49 (7): 978–985. doi:10.1038/ng.3863. PMC 5552240. PMID 28504703. Common polygenic variation, distributed across the genome, accounts for at least 20% of ASD liability. De novo single-nucleotide and copy number variants can have a strong effect on the individuals who carry them but account for less liability at a population level (<10%).
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