Gene-based analysis of regionally enriched cortical genes in GWAS data sets of cognitive traits and psychiatric disorders.
Gene-based analysis of regionally enriched cortical genes in GWAS data sets of cognitive traits and psychiatric disorders.
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DOI：
10.1371/journal.pone.0031687
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Le Hellard S
中科院分区：
文献类型：
--
作者：
Ersland KM;Christoforou A;Stansberg C;Espeseth T;Mattheisen M;Mattingsdal M;Hardarson GA;Hansen T;Fernandes CP;Giddaluru S;Breuer R;Strohmaier J;Djurovic S;Nöthen MM;Rietschel M;Lundervold AJ;Werge T;Cichon S;Andreassen OA;Reinvang I;Steen VM;Le Hellard S
尽管其估计的高遗传性，导致认知表现差异的遗传结构仍然知之甚少。不同的皮层区域在正常认知功能和障碍中起重要作用。最近，我们报告了成年大鼠大脑三个不同皮质区（前内侧、颞叶和枕叶皮质）的区域富集基因集。有人认为，基因优先或特异性地在一个区域或器官中表达反映了功能特化。采用基于基因的方法进行分析，我们使用区域富集的皮质基因来挖掘挪威认知神经遗传学（NCNG）健康成年人样本的全基因组关联研究（GWAS），以关联到9项心理测量测试措施。此外，我们探讨了严重精神疾病精神分裂症（SCZ）（n = 3个样本）和双相情感障碍（BP）（n = 3个样本）的GWAS数据集，认知障碍与之相关。 在单基因水平，颞叶皮层富集基因RAR相关孤儿受体B（RORB）显示出最强的整体关联，即与语言智力测试（词汇，P = 7.7 E-04）。 我们还应用基因集富集分析（GSEA）来测试候选基因，作为基因集，用于富集NCNG GWAS和BP和SCZ的GWAS中的关联信号。我们发现，在NCNG样本中，颞叶皮层中差异表达的基因在非语言智力（推理）的测试测量中显示出显著的关联信号富集。我们基于基因的方法表明，RORB可能参与语言智力差异，而富含颞叶皮层的基因可能对智力功能很重要，这是通过健康人群的推理测试来测量的。这些发现值得进一步复制在独立样本的认知特质。
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. 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. 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.
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影响因子：
3.7
作者：
Le Hellard S;Håvik B;Espeseth T;Breilid H;Løvlie R;Luciano M;Gow AJ;Harris SE;Starr JM;Wibrand K;Lundervold AJ;Porteous DJ;Bramham CR;Deary IJ;Reinvang I;Steen VM
通讯作者：
Steen VM
影响因子：
11
作者：
通讯作者：
--
影响因子：
4.8
作者：
Athanasiu L;Mattingsdal M;Kähler AK;Brown A;Gustafsson O;Agartz I;Giegling I;Muglia P;Cichon S;Rietschel M;Pietiläinen OP;Peltonen L;Bramon E;Collier D;Clair DS;Sigurdsson E;Petursson H;Rujescu D;Melle I;Steen VM;Djurovic S;Andreassen OA
通讯作者：
Andreassen OA
影响因子：
9.8
作者：
Cichon, Sven;Muehleisen, Thomas W.;Noethen, Markus M.
通讯作者：
Noethen, Markus M.
影响因子：
30.8
作者：
Ferreira, Manuel A. R.;O'Donovan, Michael C.;Meng, Yan A.;Jones, Ian R.;Ruderfer, Douglas M.;Jones, Lisa;Fan, Jinbo;Kirov, George;Perlis, Roy H.;Green, Elaine K.;Smoller, Jordan W.;Grozeva, Detelina;Stone, Jennifer;Nikolov, Ivan;Chambert, Kimberly;Hamshere, Marian L.;Nimgaonkar, Vishwajit L.;Moskvina, Valentina;Thase, Michael E.;Caesar, Sian;Sachs, Gary S.;Franklin, Jennifer;Gordon-Smith, Katherine;Ardlie, Kristin G.;Gabriel, Stacey B.;Fraser, Christine;Blumenstiel, Brendan;Defelice, Matthew;Breen, Gerome;Gill, Michael;Morris, Derek W.;Elkin, Amanda;Muir, Walter J.;McGhee, Kevin A.;Williamson, Richard;MacIntyre, Donald J.;MacLean, Alan W.;Clair, David St;Robinson, Michelle;Van Beck, Margaret;Pereira, Ana C. P.;Kandaswamy, Radhika;McQuillin, Andrew;Collier, David A.;Bass, Nicholas J.;Young, Allan H.;Lawrence, Jacob;Ferrier, I. Nicol;Anjorin, Adebayo;Farmer, Anne;Curtis, David;Scolnick, Edward M.;McGuffin, Peter;Daly, Mark J.;Corvin, Aiden P.;Holmans, Peter A.;Blackwood, Douglas H.;Gurling, Hugh M.;Owen, Michael J.;Purcell, Shaun M.;Sklar, Pamela;Craddock, Nick
通讯作者：
Craddock, Nick