What is the most common cause of autism?

Genetic Factors are the Most Common Cause of Autism Spectrum Disorder

The most common cause of autism spectrum disorder (ASD) is genetic factors, with multiple interacting genes contributing to the majority of cases. 1, 2

Genetic Evidence

• Twin studies demonstrate 70-90% concordance in monozygotic twins compared to only 3% in dizygotic twins, providing strong evidence for genetic heritability as the predominant causative factor 1, 2
• Sibling recurrence risk ranges from 4-8% (higher if the affected child is male), which is significantly higher than the general population prevalence 2, 1
• If a family already has two children with autism, the recurrence risk for subsequent children increases to 25-35% 2
• The calculated heritability (proportion of phenotypic variance explained by genetics) is approximately 90% 2
• Multiple genes are involved, with both common genetic variations and rare mutations contributing to risk 1
• Rare mutations with large effect sizes are the most robustly identified genetic risks for ASD 1

Specific Genetic Findings

• Chromosomal microarray analysis has a diagnostic yield of approximately 40% in suspected ASD cases 1
• The most consistently reported genetic linkages have been with chromosomal locations 15q11-13, 7q22-31, 13q, 17q11, 2q, and 16p 2
• Specific genetic conditions associated with autism include fragile X syndrome and tuberous sclerosis complex, though these account for less than 10% of cases 3
• Mutations in the MeCP2 gene are associated with Rett syndrome, which is classified under pervasive developmental disorders 3

Environmental and Other Contributing Factors

• While genetics are primary, environmental factors may interact with genetic susceptibilities 2, 1
• The prenatal period is particularly sensitive, as the developing brain is susceptible to disruptions from environmental chemicals 2, 1
• Advanced maternal and paternal age significantly increases ASD risk 1
• Extremely premature birth (<26 weeks' gestational age) is associated with increased risk 1
• Environmental chemicals that may target autism-related genes include pesticides, heavy metals, BPA, and phthalates 2, 1

Sex-Related Factors

• Males are diagnosed with ASD 3-4.5 times more frequently than females 2, 1
• The most likely explanation for male predominance involves protective factors that reduce ASD risk in females 1
• Decreased second digit-to-fourth digit ratio (indicating increased fetal testosterone exposure) is associated with ASD diagnosis 2, 1

Neurobiological Findings

• Elevated peripheral levels of serotonin is one of the most frequently replicated neurochemical findings in autism 2, 1
• Brain size increase and aberrations in white matter tract development have been observed in structural imaging studies 2, 1
• Electroencephalographic abnormalities and seizure disorders are observed in 20-25% of individuals with ASD 2

Important Caveats

• The dramatic rise in ASD prevalence (from 1 in 150 in 2002 to 1 in 59 in 2014) cannot be fully explained by genetics or changes in diagnostic criteria alone 2
• Currently, diagnosable medical conditions, cytogenetic abnormalities, and single-gene defects together account for less than 10% of cases, with the majority involving complex genetic interactions 3
• Despite extensive research, vaccines (including measles-mumps-rubella) have not been shown to cause autism 2, 3
• The complex interplay between genetic predisposition and environmental triggers makes it difficult to identify a single cause for all cases of autism 4