Heritability of autism
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.
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.
[22] 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,[22] 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.
[25] Twin studies provide a unique opportunity to explore the genetic and environmental influences on autism spectrum disorder (ASD).
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.
The study concluded that "obstetric hazards usually appear to be consequences of genetically influenced abnormal development, rather than independent aetiological factors.
It found "poorer social cognition in males", and a heritability of 0.68 with higher genetic influence in younger twins.
It also concluded that "the levels of clinical features seen in autism may be a result of mainly independent genetic traits.
[45] A 1997 study found higher rates of social and communication deficits and stereotyped behaviors in families with multiple-incidence autism.
[50] A 2001 study of brothers and parents of autistic boys looked into the phenotype in terms of one current cognitive theory of autism.
The study raised the possibility that the broader autism phenotype may include a "cognitive style" (weak central coherence) that can confer information-processing advantages.
[53] A 2005 report examined the family psychiatric history of 58 subjects with Asperger syndrome (AS) diagnosed according to DSM-IV criteria.
[54] According to a 2022 study held on 86 mother-child dyads across 18 months, "prior maternal depression didn’t predict child behavior problems later.
During this study, the population analyzed for the incidence of Autism Spectrum Disorder was restricted to those children with birth years between 1980 and 1995.
[57] Twin and family studies show that autism is a highly heritable condition, but they have left many questions for researchers, most notably: Clues to the first two questions come from studies that have shown that at least 30% of individuals with autism have spontaneous de novo mutations that occurred in the father's sperm or mother's egg that disrupt important genes for brain development.
[60][61] Tens of individual genes or mutations have been definitively identified and are cataloged by the Simons Foundation Autism Research Initiative.
In this model, no single gene directly regulates any core symptom of autism such as social behavior.
For example, one model is that many mutations affect MET and other receptor tyrosine kinases, which in turn converge on disruption of ERK and PI3K signaling.
An epigenetic model would help explain why standard genetic screening strategies have so much difficulty with autism.
[74] One hypothesis is that autism is in some sense diametrically opposite to schizophrenia and other psychotic-spectrum conditions, that alterations of genomic imprinting help to mediate the development of these two sets of conditions, and that ASD involves increased effects of paternally expressed genes, which regulate overgrowth in the brain, whereas schizophrenia involves maternally expressed genes and undergrowth.
A common hypothesis is that autism is caused by the interaction of a genetic predisposition and an early environmental insult.
[79] A 2015 study has found evidence that non-shared environmental factors has an influence on social impairments in ASD[80] Autism spectrum disorder affects all races, ethnicities, and socioeconomic groups.
Alleles linked so far strongly support the assertion that there is a large number of genotypes that are manifested as the autism phenotype.
At least some of the alleles associated with autism are fairly prevalent in the general population, which indicates they are not rare pathogenic mutations.
[118][119][120] The possibility remains that single allelic variants of the HOXA1 gene are insufficient alone to trigger the developmental events in the embryo now associated with autistic spectrum conditions.
Behavior is described as "autistic-like" and includes high tolerance to pain and habitual chewing or mouthing[130] (see also 22q13 deletion syndrome).
[134] Though not present in all individuals with autism, these mutations hold potential to illustrate some of the genetic components of spectrum disorders.
[138] A Neurexin 1 deletion has been observed occurring spontaneously in an unaffected mother and was passed on to an affected child, suggesting that the mutation has incomplete penetrance.
[153] Homozygosity mapping in pedigrees with shared ancestry and autism incidence has recently implicated the following candidate genes: PCDH10, DIA1 (formerly known as C3ORF58), NHE9, CNTN3, SCN7A, and RNF8.
