Gene discovery through imaging genetics: identification of two novel genes associated with schizophrenia
Open accessAbstract
We have discovered two genes, RSRC1 and ARHGAP18, associated with schizophrenia and in an independent study provided additional support for this association. We have both discovered and verified the association of two genes, RSRC1 and ARHGAP18, with schizophrenia. We combined a genome-wide screening strategy with neuroimaging measures as the quantitative phenotype and identified the single nucleotide polymorphisms (SNPs) related to these genes as consistently associated with the phenotypic variation. To control for the risk of false positives, the empirical P-value for association significance was calculated using permutation testing. The quantitative phenotype was Blood-Oxygen-Level Dependent (BOLD) Contrast activation in the left dorsal lateral prefrontal cortex measured during a working memory task. The differential distribution of SNPs associated with these two genes in cases and controls was then corroborated in a larger, independent sample of patients with schizophrenia (n=82) and healthy controls (n=91), thus suggesting a putative etiological function for both genes in schizophrenia. Up until now these genes have not been linked to any neuropsychiatric illness, although both genes have a function in prenatal brain development. We introduce the use of functional magnetic resonance imaging activation as a quantitative phenotype in conjunction with genome-wide association as a gene discovery tool.
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RSRC1 and MEF2C have been linked to schizophrenia and were both putatively associated with depression here.
“Additionally, associations have been found between schizophrenia and the arginine and serine rich coiled-coil 1 (RSRC1) 28 and myocyte enhancer factor 2C (MEF2C) 21 genes, both of which we found to be putatively associated with depression.”
From Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions (2019) · cites this paper as [28]
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- Authors
- Potkin, S. G., Turner, J. A., Fallon, J. A., Lakatos, A., Keator, D. B., Guffanti, G., Macciardi, F., & FBIRN
- Affiliations
- University of California, Irvine (US)
- University of Milan (IT)
- Corresponding author
- Potkin, S G
- Venue
- Molecular Psychiatry
- Published
- 2008-12-09
- Volume
- 14
- Issue
- 4
- Pages
- 416-428
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC3254586
- OpenAlex
- W2026341399
- Cited by
- 97
- References
- 70
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 11 · 2017: 9 · 2016: 3 · 2015: 5 · 2014: 7 · 2013: 8 · 2012: 8
- FWCI
- 6.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (6u54rr020278-06)
- National Center for Research Resources (U24RR021992, U54-RR020278, U54RR020278-01, P20RR020837, TIGC-P20 RR020837-01)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- schizophrenia, imaging genetics, ARHGAP18, single nucleotide polymorphisms, dorsolateral prefrontal cortex, working memory, genome-wide association study, quantitative phenotypes, permutation tests, fetal brain development, gene discovery
- MeSH terms
- Adolescent, Adult, Aged, Female, Gene Frequency, Genetic Testing, Genotype, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Nuclear Proteins, Oxygen, Schizophrenia, Prefrontal Cortex, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, GTPase-Activating Proteins, Tumor Suppressor Proteins, Genome-Wide Association Study, Young Adult
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