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

Soichiro Nakahara, Sarah Medland, Jessica A. Turner, Vince D. Calhoun, Kelvin O. Lim, Bryon A. Mueller, Juan R. Bustillo, Daniel S. O'Leary, Jatin G. Vaidya, Sarah McEwen, James Voyvodic, Aysenil Belger, Daniel H. Mathalon, Judith M. Ford, Guia Guffanti, Fabio Macciardi, Steven G. Potkin, Theo G.M. van Erp

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)393-399
Number of pages7
JournalSchizophrenia Research
Volume201
DOIs
StatePublished - Nov 2018

Bibliographical note

Funding Information:
Dr. Soichiro Nakahara's effort was supported by Astellas Pharma Inc. while he was a visiting scholar in University of California, Irvine. Dr. Bustillo consulted with Novartis and Otsuka Pharmaceuticals. Dr. Mathalon consulted for Boerhinger Ingelheim and Takeda. Dr. Potkin has financial interests in Bristol-Myers Squibb, Eisai, Inc., Eli Lilly, Forest Laboratories, Genentech, Janssen Pharmaceutical, Lundbeck, Merck, Novartis, Organon, Pfizer, Roche, Sunovion, Takeda Pharmaceutical, Vanda Pharmaceutical, Novartis, Lundbeck, Merck, Sunovion and has received grant funding from Amgen, Baxter, Bristol-Myers Squibb, Cephalon, Inc., Eli Lilly, Forest Laboratories, Genentech, Janssen Pharmaceutical, Merck, Otsuka, Pfizer, Roche, Sunovion, Takeda Pharmaceutical, Vanda Pharmaceutical, NIAAA, NIBIB, NIH/NCRR, University of Southern California, UCSF, UCSD, Baylor College of Medicine. The remaining authors declare no potential conflict of interest.

Funding Information:
This work was supported by National Institutes of Health grant numbers: NIH 1U24 RR021992 (Function Biomedical Informatics Research Network), NIH 1U24 RR025736-01 (Biomedical Informatics Research Network Coordinating Center), 5R01MH094524 , P20GM103472 , and UL1 TR000153 .

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

  • GWAS
  • MCCB
  • Neuropsychology
  • PRS
  • Schizophrenia

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