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.

• Publication year

  2018

• Venue

  Schizophrenia Research

• Publication date

  2018-11-01

• Fields of study

  Medicine, Psychology

• Identifiers
  DOI 10.1016/j.schres.2018.05.041PMID 29907492PMCID PMC6252137
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.

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• The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity.

  2008cited by this paper
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  1984cited by this paper

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