Global InformationHeritability of autism information
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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]
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]
- ^ Abrahams BS, Geschwind DH (May 2008). "Advances in autism genetics: on the threshold of a new neurobiology". Nature Reviews. Genetics. 9 (5): 341–355. doi:10.1038/nrg2346. PMC 2756414. PMID 18414403.
- ^ 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%).
- ^ Sandin S, Lichtenstein P, Kuja-Halkola R, Hultman C, Larsson H, Reichenberg A (September 2017). "The Heritability of Autism Spectrum Disorder". JAMA. 318 (12): 1182–1184. doi:10.1001/jama.2017.12141. PMC 5818813. PMID 28973605.
- ^ Buxbaum JD, Hof PR (25 October 2012). The Neuroscience of Autism Spectrum Disorders. Academic Press. ISBN 9780123919243. Retrieved 2023-07-02.
- ^ Cite error: The named reference
Freitagwas invoked but never defined (see the help page). - ^ Le Couteur A, Bailey A, Goode S, Pickles A, Robertson S, Gottesman I, Rutter M (October 1996). "A broader phenotype of autism: the clinical spectrum in twins". Journal of Child Psychology and Psychiatry, and Allied Disciplines. 37 (7): 785–801. doi:10.1111/j.1469-7610.1996.tb01475.x. eISSN 1469-7610. ISSN 0021-9630. OCLC 01307942. PMID 8923222.
- ^ Folstein SE, Rosen-Sheidley B (December 2001). "Genetics of autism: complex aetiology for a heterogeneous disorder". Nature Reviews. Genetics. 2 (12): 943–55. doi:10.1038/35103559. PMID 11733747. S2CID 9331084.
- ^ Cite error: The named reference
Boltonwas invoked but never defined (see the help page). - ^ Sykes NH, Lamb JA (September 2007). "Autism: the quest for the genes". Expert Reviews in Molecular Medicine. 9 (24): 1–15. doi:10.1017/S1462399407000452. PMID 17764594. S2CID 45880191.
- ^ Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017-05-22). "Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia". Molecular Autism. 8 (1): 21. doi:10.1186/s13229-017-0137-9. ISSN 2040-2392. PMC 5441062. PMID 28540026.
- ^ Persico AM, Bourgeron T (July 2006). "Searching for ways out of the autism maze: genetic, epigenetic and environmental clues". Trends in Neurosciences. 29 (7): 349–358. doi:10.1016/j.tins.2006.05.010. PMID 16808981. S2CID 26722022.
- ^ Yang MS, Gill M (April 2007). "A review of gene linkage, association and expression studies in autism and an assessment of convergent evidence". International Journal of Developmental Neuroscience. 25 (2): 69–85. doi:10.1016/j.ijdevneu.2006.12.002. PMID 17236739. S2CID 39503634.
- ^ Cohen D, Pichard N, Tordjman S, Baumann C, Burglen L, Excoffier E, et al. (February 2005). "Specific genetic disorders and autism: clinical contribution towards their identification". Journal of Autism and Developmental Disorders. 35 (1): 103–16. doi:10.1007/s10803-004-1038-2. PMID 15796126. S2CID 2101244.
- ^ Müller RA (2007). "The study of autism as a distributed disorder". Mental Retardation and Developmental Disabilities Research Reviews. 13 (1): 85–95. doi:10.1002/mrdd.20141. PMC 3315379. PMID 17326118.
- ^ Cook EH, Scherer SW (October 2008). "Copy-number variations associated with neuropsychiatric conditions". Nature. 455 (7215): 919–923. Bibcode:2008Natur.455..919C. doi:10.1038/nature07458. PMID 18923514. S2CID 4377899.
- ^ Gai X, Xie HM, Perin JC, Takahashi N, Murphy K, Wenocur AS, et al. (April 2012). "Rare structural variation of synapse and neurotransmission genes in autism". Molecular Psychiatry. 17 (4): 402–411. doi:10.1038/mp.2011.10. PMC 3314176. PMID 21358714.
- ^ Devlin B, Scherer SW (June 2012). "Genetic architecture in autism spectrum disorder". Current Opinion in Genetics & Development. Molecular and genetic bases of disease. 22 (3): 229–237. doi:10.1016/j.gde.2012.03.002. PMID 22463983.
- ^ Sztainberg Y, Zoghbi HY (October 2016). "Lessons learned from studying syndromic autism spectrum disorders". Nature Neuroscience. 19 (11): 1408–1417. doi:10.1038/nn.4420. PMID 27786181. S2CID 3332899.
- ^ Benvenuto A, Moavero R, Alessandrelli R, Manzi B, Curatolo P (August 2009). "Syndromic autism: causes and pathogenetic pathways". World Journal of Pediatrics. 5 (3): 169–176. doi:10.1007/s12519-009-0033-2. PMID 19693459. S2CID 27851799.
- ^ a b Beaudet AL (May 2007). "Autism: highly heritable but not inherited". Nature Medicine. 13 (5): 534–6. doi:10.1038/nm0507-534. PMID 17479094. S2CID 11673879.
- ^ Tabor HK, Cho MK (September 2007). "Ethical implications of array comparative genomic hybridization in complex phenotypes: points to consider in research". Genetics in Medicine. 9 (9): 626–31. doi:10.1097/GIM.0b013e3181485688. PMC 2220022. PMID 17873651.
- ^ Cite error: The named reference
AGPC2007was invoked but never defined (see the help page). - ^ Liu XQ, Paterson AD, Szatmari P (October 2008). "Genome-wide linkage analyses of quantitative and categorical autism subphenotypes". Biological Psychiatry. 64 (7): 561–70. doi:10.1016/j.biopsych.2008.05.023. PMC 2670970. PMID 18632090.