Genetic and environmental factors contributing to autism spectrum disorder: A comparative study

Roughly 1.7% of children in Sweden receive an autism spectrum disorder diagnosis before age 10, but the relative weight of genetic versus environmental contributors remains a matter of active debate. This research compared the contributions of heritable genetic factors, prenatal and perinatal environmental exposures, and gene-environment interactions to ASD liability in a Swedish population-based cohort. Data were drawn from the Swedish National Patient Register and the Swedish Twin Registry, encompassing 4,832 individuals diagnosed with ASD and 14,496 matched controls, all born between 2000 and 2018. Genetic liability was estimated through twin concordance analyses and polygenic risk scoring derived from genome-wide association data. Environmental exposures assessed included advanced parental age, prenatal infections, air pollution levels (PM2.5), pesticide proximity, folic acid supplementation status, preterm birth, and low birth weight.Twin-based heritability for the broad ASD phenotype was estimated at 0.81 (95% CI: 0.74-0.87), while SNP-based heritability was 0.43 (95% CI: 0.37-0.49), indicating that common genetic variants explain roughly half the heritable variance. Among environmental factors, preterm birth (OR = 2.13, 95% CI: 1.78-2.51) and prenatal infection (OR = 1.89, 95% CI: 1.54-2.29) showed the strongest independent associations with ASD. Gene-environment interaction analyses revealed that children carrying high polygenic risk who were also exposed to prenatal infection had a 3.7-fold increased likelihood of ASD compared to low-risk, unexposed children (95% CI: 2.81-4.92). Subphenotype analyses indicated differential heritability patterns: social communication difficulties showed the highest twin-based heritability (h² = 0.83), while language ability showed the lowest (h² = 0.64), suggesting that environmental factors play a larger role in shaping language outcomes.Shared environmental factors accounted for 8.7% of total variance, non-shared environmental factors for 14.2%, and gene-environment interactions for an estimated 7.9%. These findings confirm that ASD is predominantly genetic in origin but highlight that environmental exposures, particularly during the prenatal period, can meaningfully modify risk, especially among genetically vulnerable individuals. The results support a multifactorial model of ASD causation and suggest that targeted prenatal health measures could reduce ASD incidence among high-risk populations.