The impact of genome-wide supported schizophrenia risk variants in the neurogranin gene on brain structure and function.

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 t...

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Autores principales: 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
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:f10acb323e0242a2af7a568cc9f561542021-11-18T08:52:53ZThe impact of genome-wide supported schizophrenia risk variants in the neurogranin gene on brain structure and function.1932-620310.1371/journal.pone.0076815https://doaj.org/article/f10acb323e0242a2af7a568cc9f561542013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24098564/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Esther WaltonDaniel GeislerJohanna HassJingyu LiuJessica TurnerAnastasia YendikiMichael N SmolkaBeng-Choon HoDara S ManoachRandy L GollubVeit RoessnerVince D CalhounStefan EhrlichPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e76815 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
The impact of genome-wide supported schizophrenia risk variants in the neurogranin gene on brain structure and function.
description 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.
format article
author 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
author_facet 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
author_sort Esther Walton
title The impact of genome-wide supported schizophrenia risk variants in the neurogranin gene on brain structure and function.
title_short The impact of genome-wide supported schizophrenia risk variants in the neurogranin gene on brain structure and function.
title_full The impact of genome-wide supported schizophrenia risk variants in the neurogranin gene on brain structure and function.
title_fullStr The impact of genome-wide supported schizophrenia risk variants in the neurogranin gene on brain structure and function.
title_full_unstemmed The impact of genome-wide supported schizophrenia risk variants in the neurogranin gene on brain structure and function.
title_sort impact of genome-wide supported schizophrenia risk variants in the neurogranin gene on brain structure and function.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/f10acb323e0242a2af7a568cc9f56154
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