- Autism is highly heritable. Evidence:
- Twin studies.
- A recent large twin study suggests genes and environment both contribute, but some methodological issues (e.g. differences in heritability between girls and boys) drove the genetic contribution artifactually down
- Studies of heritability of quantitative traits
- Caveats about heritability:
- The amount of genetic contribution plus the amount of environmental contribution does not have to add up to 100%.
- Autism may be heritable but not inherited due to “de novo mutations” — changes in genes in affected individuals that their parents did not have
- If genes cause autism, how do they do that?
- Direct influence on brain development and brain structure
- Direct influence on brain function, through genetic influence upon
- Synaptic function
- Neurotransmitters and receptors
- Other aspects of brain function, such as brain networks
- Indirect influence on brain function
- Direct impact on other things (like physiology) that affect brain development or function
- Examples: genetic influence on brain energetics (mitochondria) can impact synaptic function since synapses require large amounts of energy
- Creating vulnerability in other ways so that other things can more easily influence brain function
Other processes that involve genes or DNA but are not strictly about gene mutations:
- Epigenetics: the study of functionally relevant heritable changes in the genome that are not due to changes in the sequence of DNA nucleotides that make up the genetic code. A growing number of papers are exploring epigenetics and autism.
- Non-coding DNA: Most of our DNA does not code for proteins. In recent years people have stopped calling this “junk DNA” as functions it serves (such as regulation of gene function) have been identified
- Ways genes and environment can interact (schema from Corrales and Herbert 2011)
- Genetic damage
- Epigenetic damage
- Gene-environment correlation (impact of genotype on one’s environment or exposures)
- Gene x environment interactions: genetic susceptibility, where the impact of environmental exposures differs depending on genotype
- Environmental genomics: Study of how genetic variability can influence or predict environmental susceptibility. The Environmental Genome Project of the NIEHS is a major example of this approach.
