Causes of Autism - Genetics

Genetics

Genetic factors may be the most significant cause for autism spectrum disorders. Early studies of twins had estimated heritability to be over 90%, meaning that genetics explains over 90% of whether a child will develop autism. However, this may be an overestimate, as new twin data and models with structural genetic variation are needed. Many of the non-autistic co-twins had learning or social disabilities. For adult siblings the risk for having one or more features of the broader autism phenotype might be as high as 30%.

The genetics of autism are complex. Linkage analysis has been inconclusive; many association analyses have had inadequate power. More than one gene may be implicated, different genes may be involved in different individuals, and the genes may interact with each other or with environmental factors. Several candidate genes have been located, but the mutations that increase autism risk have not been identified for most candidate genes. A substantial fraction of autism may be highly heritable but not inherited because the mutation that causes the autism is not present in the parental genome. One hypothesis is that autism is in some sense diametrically opposite to schizophrenia, and that autism involves increased effects via genomic imprinting of paternally expressed genes that regulate overgrowth in the brain, whereas schizophrenia involves maternally expressed genes and undergrowth.

Though autism's genetic factors explain most of the risk of developing autism, they do not explain all of it. A common hypothesis is that autism is caused by the interaction of a genetic predisposition and an early environmental insult. Several theories based on environmental factors have been proposed to address the remaining risk. Some of these theories focus on prenatal environmental factors, such as agents that cause birth defects, and others focus on the environment after birth, such as children's diets.

Risk factors for autism include parental characteristics such as advanced maternal age and advanced paternal age. The risk is greater for advanced paternal age. One hypothesis is that this is caused by older sperm that have greater mutation burden, and another is that men who carry more genetic liability have some features of autism and therefore marry and have children later. These two hypotheses are not mutually exclusive.