Ultra-rare disruptive and damaging mutations influence educational attainment in the general population

Disruptive and damaging ultra-rare variants (URVs) in highly constrained (HC) genes are enriched in individuals with neurodevelopmental disorders. In the general population, this class of variants was associated with a decrease in years of education (YOE; −3.1 months; P-value=3.3×10−8). This effect was stronger among high brain-expressed genes and explained more YOE variance than pathogenic copy number variation, but less than common variants. Disruptive and damaging URVs in HC genes influence the determinants of YOE in the general population.