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

Authors

Esther Walton, Technische Universitat DresdenFollow
Daniel Geisler, Technische Universitat DresdenFollow
Johanna Hass, Technische Universitat DresdenFollow
Jingyu Liu, University of New MexicoFollow
Jessica Turner, Georgia State UniversityFollow
Anastasia Yendiki, Massachusetts General HospitalFollow
Michael N. Smolka, Technische Universitat DresdenFollow
Beng-Choon Ho, University of IowaFollow
Dara S. Manoach, Massachusetts General HospitalFollow
Randy L. Gollub, Massachusetts General HospitalFollow
Veit Roessner, Technische Universitat DresdenFollow
Vince D. Calhoun, University of New MexicoFollow
Stefan Ehrlich, Technische Universitat DresdenFollow

Document Type

Article

Publication Date

10-2013

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 memoryelicited 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 brainbased 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.

Comments

Originally Published in:

PLoS ONE 8(10): e76815. doi:http://dx.doi.org/10.1371/journal.pone.0076815

Recommended Citation

Walton E, Geisler D, Hass J, Liu J, Turner J, et al. (2013) The Impact of Genome-Wide Supported Schizophrenia Risk Variants in the Neurogranin Gene on Brain Structure and Function. PLoS ONE 8(10): e76815. doi:http://dx.doi.org/10.1371/journal.pone.0076815

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This work is licensed under a Creative Commons Attribution 4.0 International License.