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We then tested, in a sample of 808 patients and 192 controls, whether these risk scores were associated with altered performance on cognitive functions known to be affected in schizophrenia. A subgroup of healthy participants also underwent functional imaging during memory (<jats:italic>n</jats:italic>=108) and face processing tasks (<jats:italic>n</jats:italic>=83). Increased polygenic risk within the empirically derived miR-137 regulated gene score was associated with significantly lower performance on intelligence quotient, working memory and episodic memory. These effects were observed most clearly at a polygenic threshold of <jats:italic>P</jats:italic>=0.05, although significant results were observed at all three thresholds analyzed. This association was found independently for the gene set as a whole, excluding the schizophrenia-associated <jats:italic>MIR137</jats:italic> SNP itself. Analysis of the spatial working memory fMRI task further suggested that increased risk score (thresholded at <jats:italic>P</jats:italic>=10<jats:sup>−5</jats:sup>) was significantly associated with increased activation of the right inferior occipital gyrus. 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As microRNA-137 is known to regulate the expression of ~1900 other genes, including several that are independently associated with schizophrenia, we tested whether this gene set was also associated with variation in cognitive performance. Our analysis was based on an empirically derived list of genes whose expression was altered by manipulation of <jats:italic>MIR137</jats:italic> expression. This list was cross-referenced with genome-wide schizophrenia association data to construct individual polygenic scores. We then tested, in a sample of 808 patients and 192 controls, whether these risk scores were associated with altered performance on cognitive functions known to be affected in schizophrenia. A subgroup of healthy participants also underwent functional imaging during memory (<jats:italic>n</jats:italic>=108) and face processing tasks (<jats:italic>n</jats:italic>=83). 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