Gene discovery through imaging genetics: identification of two novel genes associated with schizophrenia
Open Access
- 9 December 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Psychiatry
- Vol. 14 (4), 416-428
- https://doi.org/10.1038/mp.2008.127
Abstract
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.This publication has 70 references indexed in Scilit:
- A Genome Screen for Quantitative Trait Loci Influencing Schizophrenia and Neurocognitive PhenotypesAmerican Journal of Psychiatry, 2008
- Multivariate analyses suggest genetic impacts on neurocircuitry in schizophreniaNeuroReport, 2008
- Neuroimaging and molecular genetics of schizophrenia: pathophysiological advances and therapeutic potentialBritish Journal of Pharmacology, 2008
- WGAViewer: Software for genomic annotation of whole genome association studies: Figure 1.Genome Research, 2008
- Two independent alleles at 6q23 associated with risk of rheumatoid arthritisNature Genetics, 2007
- PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage AnalysesAmerican Journal of Human Genetics, 2007
- A tutorial on statistical methods for population association studiesNature Reviews Genetics, 2006
- Principal components analysis corrects for stratification in genome-wide association studiesNature Genetics, 2006
- Complement Factor H Polymorphism in Age-Related Macular DegenerationScience, 2005
- Statistical significance for genomewide studiesProceedings of the National Academy of Sciences of the United States of America, 2003