Gene-Based Analysis of Regionally Enriched Cortical Genes in GWAS Data Sets of Cognitive Traits and Psychiatric Disorders
| Autor: | Carla P. D. Fernandes, Christine Stansberg, Vidar M. Steen, Manuel Mattheisen, Jana Strohmaier, Marcella Rietschel, Ivar Reinvang, Markus M. Nöthen, Andrea Christoforou, Thomas Werge, Gudmundur A. Hardarson, René Breuer, Thomas Espeseth, Sven Cichon, Morten Mattingsdal, Srdjan Djurovic, Kari Merete Ersland, Thomas Hansen, Sudheer Giddaluru, Astri J. Lundervold, Ole A. Andreassen, Stephanie Le Hellard |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Candidate gene Bipolar Disorder Heredity Genome-wide association study genetics [Cognition Disorders] pathology [Frontal Lobe] genetics [Mental Disorders] Cognition 0302 clinical medicine genetics [Schizophrenia] pathology [Occipital Lobe] Cerebral Cortex Psychiatry Temporal cortex 0303 health sciences Multidisciplinary Norway Mental Disorders physiology [Cognition] Middle Aged Verbal reasoning Temporal Lobe Frontal Lobe Mental Health Schizophrenia Medicine Female ddc:500 Occipital Lobe Research Article Adult medicine.medical_specialty Adolescent Cognitive Neuroscience Science Neurogenetics Cognitive neuroscience Biology 03 medical and health sciences Genetics medicine Animals Humans ddc:610 Aged 030304 developmental biology Models Genetic metabolism [Cerebral Cortex] Human Genetics pathology [Temporal Lobe] medicine.disease Rats Case-Control Studies Cognition Disorders genetics [Bipolar Disorder] 030217 neurology & neurosurgery Neuroscience Genome-Wide Association Study |
| Zdroj: | PLOS ONE 7(2), e31687 (2012). doi:10.1371/journal.pone.0031687 PLoS ONE, Vol 7, Iss 2, p e31687 (2012) PLoS ONE PLoS one 7(2), e31687 (2012). doi:10.1371/journal.pone.0031687 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0031687 |
| Popis: | BackgroundDespite its estimated high heritability, the genetic architecture leading to differences in cognitive performance remains poorly understood. Different cortical regions play important roles in normal cognitive functioning and impairment. Recently, we reported on sets of regionally enriched genes in three different cortical areas (frontomedial, temporal and occipital cortices) of the adult rat brain. It has been suggested that genes preferentially, or specifically, expressed in one region or organ reflect functional specialisation. Employing a gene-based approach to the analysis, we used the regionally enriched cortical genes to mine a genome-wide association study (GWAS) of the Norwegian Cognitive NeuroGenetics (NCNG) sample of healthy adults for association to nine psychometric tests measures. In addition, we explored GWAS data sets for the serious psychiatric disorders schizophrenia (SCZ) (n = 3 samples) and bipolar affective disorder (BP) (n = 3 samples), to which cognitive impairment is linked.Principal findingsAt the single gene level, the temporal cortex enriched gene RAR-related orphan receptor B (RORB) showed the strongest overall association, namely to a test of verbal intelligence (Vocabulary, P = 7.7E-04). We also applied gene set enrichment analysis (GSEA) to test the candidate genes, as gene sets, for enrichment of association signal in the NCNG GWAS and in GWASs of BP and of SCZ. We found that genes differentially expressed in the temporal cortex showed a significant enrichment of association signal in a test measure of non-verbal intelligence (Reasoning) in the NCNG sample.ConclusionOur gene-based approach suggests that RORB could be involved in verbal intelligence differences, while the genes enriched in the temporal cortex might be important to intellectual functions as measured by a test of reasoning in the healthy population. These findings warrant further replication in independent samples on cognitive traits. |
| Databáze: | OpenAIRE |
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