Risk for Autism Across Generations

Area of Science:

• Genetics and Genomics
• Developmental Neuroscience
• Public Health

Background:

• Autism spectrum disorder (ASD) exhibits complex inheritance, with a male predominance.
• Etiological models implicate common and rare genetic variations in ASD risk.
• A hypothesis suggests inherited rare variations contribute to risk across generations, particularly via female lineage.

Purpose of the Study:

• To investigate the multi-generational transmission of autism spectrum disorder (ASD) risk.
• To examine the role of parental age across generations in relation to ASD diagnosis in offspring.
• To test the hypothesis of inherited risk factors, especially through female lineage.

Main Methods:

• Analysis of combined national register data from Sweden, Denmark, and Finland (12.6 million individuals).
• Inclusion of parental age information across two generations.
• Assessment of autism spectrum disorder (ASD) diagnosis in the third generation.

Main Results:

• Increased paternal age at daughter's birth correlated with higher ASD risk in the next generation.
• No association found between increased paternal age at son's birth and ASD risk in offspring.
• Young maternal age at birth was associated with increased ASD risk in offspring.

Conclusions:

• Etiological risk factors for ASD may span multiple generations.
• Findings suggest distinct genetic and non-genetic mechanisms underlying multi-generational ASD risk.
• Further research into trans-generational risk factors for autism is warranted.