The Impact of Genome-Wide Supported Schizophrenia Risk Variants in the Neurogranin Gene on Brain Structure and Function

Walton, Esther; Geisler, Daniel; Hass, Johanna; Liu, Jingyu; Turner, Jessica; Yendiki, Anastasia; Smolka, Michael N.; Ho, Beng-Choon; Manoach, Dara S.; Gollub, Randy L.; Roessner, Veit; Calhoun, Vince D.; Ehrlich, Stefan

doi:10.1371/journal.pone.0076815

The Impact of Genome-Wide Supported Schizophrenia Risk Variants in the Neurogranin Gene on Brain Structure and Function

Journal Article · Wed Oct 02 00:00:00 EDT 2013 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0076815· OSTI ID:1904567

Walton, Esther ^[1]; Geisler, Daniel ^[2]; Hass, Johanna ^[2]; Liu, Jingyu ^[3]; Turner, Jessica ^[4]; Yendiki, Anastasia ^[5]; Smolka, Michael N. ^[6]; Ho, Beng-Choon ^[7]; Manoach, Dara S. ^[8]; Gollub, Randy L. ^[8]; Roessner, Veit ^[2]; Calhoun, Vince D. ^[3]; Ehrlich, Stefan ^[9]

Dresden University of Technology (Germany); Dresden Univ. of Technology (Germany)
Dresden University of Technology (Germany)
MIND Research Network, Albuquerque, NM (United States); University of New Mexico, Albuquerque, NM (United States)
MIND Research Network, Albuquerque, NM (United States)
Massachusetts General Hospital, Charlestown, MA (United States)
University of Technology, Dresden (Germany)
University of Iowa, Iowa City, IA (United States)
Massachusetts General Hospital, Charlestown, MA (United States); Massachusetts General Hospital, Boston, MA (United States)
Dresden University of Technology (Germany); Massachusetts General Hospital, Charlestown, MA (United States); Massachusetts General Hospital, Boston, MA (United States)

The neural mechanisms underlying genetic risk for schizophrenia, a highly heritable psychiatric condition, are still under investigation. New schizophrenia risk genes discovered through genome-wide association studies (GWAS), such as neurogranin (NRGN), can be used to identify these mechanisms. In this study we examined the association of two common NRGN risk single nucleotide polymorphisms (SNPs) with functional and structural brain-based intermediate phenotypes for schizophrenia. We obtained structural, functional MRI and genotype data of 92 schizophrenia patients and 114 healthy volunteers from the multisite Mind Clinical Imaging Consortium study. Two schizophrenia-associated NRGN SNPs (rs12807809 and rs12541) were tested for association with working memory elicited dorsolateral prefrontal cortex (DLPFC) activity and surface-wide cortical thickness. NRGN rs12541 risk allele homozygotes (TT) displayed increased working memory-related activity in several brain regions, including the left DLPFC, left insula, left somatosensory cortex and the cingulate cortex, when compared to non-risk allele carriers. NRGN rs12807809 non-risk allele (C) carriers showed reduced cortical gray matter thickness compared to risk allele homozygotes (TT) in an area comprising the right pericalcarine gyrus, the right cuneus, and the right lingual gyrus. Our study highlights the effects of schizophrenia risk variants in the NRGN gene on functional and structural brain-based intermediate phenotypes for schizophrenia. These results support recent GWAS findings and further implicate NRGN in the pathophysiology of schizophrenia by suggesting that genetic NRGN risk variants contribute to subtle changes in neural functioning and anatomy that can be quantified with neuroimaging methods.

View Accepted Manuscript (DOE)

Research Organization:: University of California, Davis, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH); Mind Research Network; German Research Foundation (DFG); NARSAD Young Investigator; Friedrich-Ebert Stiftung

Grant/Contract Number:: FG02-99ER62764

OSTI ID:: 1904567

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 10 Vol. 8; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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The Impact of Genome-Wide Supported Schizophrenia Risk Variants in the Neurogranin Gene on Brain Structure and Function

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