Polygenic risk score, genome-wide association, and gene set analyses of cognitive domain deficits in schizophrenia
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Updated: Feb 8, 2026

A Pathway Association Study Tool for GWAS Analyses of Metabolic Pathway Information
Published on: July 1, 2020
Soichiro Nakahara1, Sarah Medland2, Jessica A Turner3
1Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA 92617, United States; Unit 2, Candidate Discovery Science Labs, Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Abstract:
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.
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