Polygenic risk score, genome-wide association, and gene set analyses of cognitive domain deficits in schizophrenia.

This study assessed genetic contributions to six cognitive domains, identified by the MATRICS Cognitive Consensus Battery as relevant for schizophrenia, cognition-enhancing, clinical trials. Psychiatric Genomics Consortium Schizophrenia polygenic risk scores showed significant negative correlations with each cognitive domain. Genome-wide association analyses identified loci associated with attention/vigilance (rs830786 within HNF4G), verbal memory (rs67017972 near NDUFS4), and reasoning/problem solving (rs76872642 within HDAC9). Gene set analysis identified unique and shared genes across cognitive domains. These findings suggest involvement of common and unique mechanisms across cognitive domains and may contribute to the discovery of new therapeutic targets to treat cognitive deficits in schizophrenia.

2 Alaskan native ancestry schizophrenia cases, 18 Asian ancestry schizophrenia cases, 20 African American schizophrenia cases, 1 Native Hawaiian ancestry schizophrenia cases, 86 European ancestry schizophrenia cases, 2 Alaskan native ancestry controls, 10 Asian ancestry controls, 17 African American controls, 1 Native Hawaiian ancestry controls, 106 European ancestry controls