Investigating Sex Differences in Heritability of Autism Spectrum Disorder

There is variation in the heritability of autism spectrum disorder (ASD) between males and females, according to a study published in JAMA Psychiatry.

This population-based, retrospective study utilized national health register data of non-twin siblings and cousins from Sweden between January 1, 1985, and December 31, 1998. Participants were followed up to age 19. In total, 1,047,649 individuals (from 456,832 families) were included.

Regarding diagnosis of ASD in Sweden, the authors noted, “At age 4 years, a mandatory developmental assessment (motor, language, cognitive, and social) is conducted. Children with suspected developmental disorders are referred to a specialized team in a child psychiatry unit or habilitation service.” Diagnoses are then reported to the National Patient Register.

The rate of diagnosed ASD in the entire sample was 1.17%. The incidence was 1.51% in males and 0.80% in females. Heritability was estimated at 87.0% for males (95% CI, 81.4%-92.6%) and 75.7% for females (95% CI, 68.4%-83.1%); the difference was 11.3% (95% CI, 1.0%-21.6%). Adjusting for gestational age did not impact heritability.

The authors acknowledged other risk sources that could influence ASD diagnoses outside of heritability, including environmental factors, differences in cultural environment that could lead to diagnosis differences, genetic sources that are not inherited additively, or even deficits in the model utilized to estimate heritability. They also noted clinical behavioral factors, such as female-typical autism presentation, could influence the rate of ASD diagnosis. “The norms in diagnostic procedures and societal changes across time may have affected males and females differently,” they noted.

“Based on population-based data from Sweden, this cohort study found that genetic variability in ASD liability differs between males and females, indicating that some of the underlying causes of the condition may differ between the 2 sexes,” the authors wrote. They called for further research to explore the relationship of gene-environment interactions and to investigate the differences in heritability between sexes with consideration for ASD severity, co-occurring conditions, and age at first diagnosis.