Gene-based analysis of regionally enriched cortical genes in GWAS data sets of cognitive traits and psychiatric disorders.
<h4>Background</h4>Despite 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...
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oai:doaj.org-article:8fc382b6d0cf4619a980614c796de04e2021-11-18T07:27:06ZGene-based analysis of regionally enriched cortical genes in GWAS data sets of cognitive traits and psychiatric disorders.1932-620310.1371/journal.pone.0031687https://doaj.org/article/8fc382b6d0cf4619a980614c796de04e2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22384057/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Despite 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.<h4>Principal findings</h4>At 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.<h4>Conclusion</h4>Our 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.Kari M ErslandAndrea ChristoforouChristine StansbergThomas EspesethManuel MattheisenMorten MattingsdalGudmundur A HardarsonThomas HansenCarla P D FernandesSudheer GiddaluruRené BreuerJana StrohmaierSrdjan DjurovicMarkus M NöthenMarcella RietschelAstri J LundervoldThomas WergeSven CichonOle A AndreassenIvar ReinvangVidar M SteenStephanie Le HellardPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31687 (2012) |
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| spellingShingle |
Medicine R Science Q Kari M Ersland Andrea Christoforou Christine Stansberg Thomas Espeseth Manuel Mattheisen Morten Mattingsdal Gudmundur A Hardarson Thomas Hansen Carla P D Fernandes Sudheer Giddaluru René Breuer Jana Strohmaier Srdjan Djurovic Markus M Nöthen Marcella Rietschel Astri J Lundervold Thomas Werge Sven Cichon Ole A Andreassen Ivar Reinvang Vidar M Steen Stephanie Le Hellard Gene-based analysis of regionally enriched cortical genes in GWAS data sets of cognitive traits and psychiatric disorders. |
| description |
<h4>Background</h4>Despite 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.<h4>Principal findings</h4>At 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.<h4>Conclusion</h4>Our 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. |
| format |
article |
| author |
Kari M Ersland Andrea Christoforou Christine Stansberg Thomas Espeseth Manuel Mattheisen Morten Mattingsdal Gudmundur A Hardarson Thomas Hansen Carla P D Fernandes Sudheer Giddaluru René Breuer Jana Strohmaier Srdjan Djurovic Markus M Nöthen Marcella Rietschel Astri J Lundervold Thomas Werge Sven Cichon Ole A Andreassen Ivar Reinvang Vidar M Steen Stephanie Le Hellard |
| author_facet |
Kari M Ersland Andrea Christoforou Christine Stansberg Thomas Espeseth Manuel Mattheisen Morten Mattingsdal Gudmundur A Hardarson Thomas Hansen Carla P D Fernandes Sudheer Giddaluru René Breuer Jana Strohmaier Srdjan Djurovic Markus M Nöthen Marcella Rietschel Astri J Lundervold Thomas Werge Sven Cichon Ole A Andreassen Ivar Reinvang Vidar M Steen Stephanie Le Hellard |
| author_sort |
Kari M Ersland |
| title |
Gene-based analysis of regionally enriched cortical genes in GWAS data sets of cognitive traits and psychiatric disorders. |
| title_short |
Gene-based analysis of regionally enriched cortical genes in GWAS data sets of cognitive traits and psychiatric disorders. |
| title_full |
Gene-based analysis of regionally enriched cortical genes in GWAS data sets of cognitive traits and psychiatric disorders. |
| title_fullStr |
Gene-based analysis of regionally enriched cortical genes in GWAS data sets of cognitive traits and psychiatric disorders. |
| title_full_unstemmed |
Gene-based analysis of regionally enriched cortical genes in GWAS data sets of cognitive traits and psychiatric disorders. |
| title_sort |
gene-based analysis of regionally enriched cortical genes in gwas data sets of cognitive traits and psychiatric disorders. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/8fc382b6d0cf4619a980614c796de04e |
| work_keys_str_mv |
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