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

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

doi:10.1371/journal.pone.0076815

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

Esther Walton, Daniel Geisler, Johanna Hass, Jingyu Liu, Jessica Turner, Anastasia Yendiki, Michael N. Smolka, Beng-Choon Ho, Dara S. Manoach, Randy L. Gollub, …

PloS one, Vol.8(10), pp.No. e76815-e76815

10/02/2013

DOI: 10.1371/journal.pone.0076815

PMCID: PMC3788740

PMID: 24098564

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Abstract

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.

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Title: Subtitle: The Impact of Genome-Wide Supported Schizophrenia Risk Variants in the Neurogranin Gene on Brain Structure and Function
Creators: Esther Walton - Technische Universität Dresden
Daniel Geisler - Technische Universität Dresden
Johanna Hass - Technische Universität Dresden
Jingyu Liu - University of New Mexico
Jessica Turner - Mind Research Network
Anastasia Yendiki - Harvard University
Michael N. Smolka - Technische Universität Dresden
Beng-Choon Ho - University of Iowa
Dara S. Manoach - University of Iowa
Randy L. Gollub - University of Iowa
Veit Roessner - Technische Universität Dresden
Vince D. Calhoun - University of New Mexico
Stefan Ehrlich - Technische Universität Dresden
Resource Type: Journal article
Publication Details: PloS one, Vol.8(10), pp.No. e76815-e76815
DOI: 10.1371/journal.pone.0076815
PMID: 24098564
PMCID: PMC3788740
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library Science
Number of pages: 11
Grant note: R01MH067720 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) 1RC1MH089257; 2 R01MH067720 / NIMH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) P41RR14075 / National Institutes of Health (NIH/NCRR); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) MO1 RR025758-01 / NIH.NCRR; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) U24RR021992 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) K99/R00 / NIH/NIBIB; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB) NARSAD Young Investigator Grant; NARSAD U24RR021992 / Function BIRN Friedrich-Ebert Stiftung DE-FG02-99ER62764 / Department of Energy; United States Department of Energy (DOE) 1U24; RR021382A / Mind Research Network, Morphometry BIRN Deutsche Forschungsgemeinschaft; German Research Foundation (DFG) K99EB008129 / NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB)
Language: English
Date published: 10/02/2013
Academic Unit: Psychiatry
Record Identifier: 9984280878202771

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