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The impact of rare protein coding genetic variation on adult cognitive function

Compelling evidence suggests that cognitive function is strongly influenced by genetics. Here, we conduct a large-scale exome study to examine whether rare protein coding variants impact cognitive function in the adult population (N=485,930). We identify eight genes associated with adult cognitive function through rare coding variants with large effects. We demonstrate how the dosage of a single gene, KDM5B, may determine the variability of cognitive, behavioral, and molecular traits in mice and humans. We further provide evidence that rare and common variants overlap in association signals and contribute additively to cognitive function. Our findings uncover a contribution of rare coding variants to cognitive function and highlight that the spectrum of cognitive function in the normal adult population is influenced by the action of single genes.