Most genetic risk for autism resides with common variation

Area of Science:

• Genetics
• Psychiatry
• Epidemiology

Background:

• The genetic basis of autism spectrum disorder (autism) is complex, involving both rare and common genetic variations.
• Previous research identified individual risk genes from rare variations, like de novo mutations, suggesting their dominance.
• Emerging evidence indicates common genetic variations, though individually small in effect, collectively contribute significantly to autism risk.

Purpose of the Study:

• To clarify the relative contributions of rare and common genetic variations to the overall heritability of autism.
• To quantify the proportion of autism's genetic variance attributable to common versus rare variations.

Main Methods:

• Utilized a unique epidemiological sample from Sweden.
• Employed novel statistical methods to differentiate total narrow-sense heritability from heritability due to common variations.
• Synthesized findings with results from existing autism genetics studies.

Main Results:

• The total narrow-sense heritability for autism is estimated at approximately 52.4%.
• The majority of this heritability is attributed to common genetic variations.
• Rare de novo mutations contribute significantly to individual susceptibility but account for a modest 2.6% of the total variance in liability.

Conclusions:

• Common genetic variations play a predominant role in the genetic architecture of autism.
• While rare de novo mutations are important for individual risk, their impact on the overall genetic variance of autism is less than that of common variations.
• Understanding the allelic spectrum in autism requires considering the substantial collective impact of common variations alongside the individual impact of rare variations.