A meta-analysis of gene expression quantitative trait loci in brain.
A meta-analysis of gene expression quantitative trait loci in brain.
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DOI：
10.1038/tp.2014.96
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发表时间：
2014-10-07
影响因子：
6.8
通讯作者：
Sullivan PF
中科院分区：
文献类型：
--
作者：
Kim Y;Xia K;Tao R;Giusti-Rodriguez P;Vladimirov V;van den Oord E;Sullivan PF
目前的大脑表达数量性状位点 (eQTL) 目录不完整，研究结果不能很好地重复。所有现有的皮质 eQTL 研究规模都很小，并且强调荟萃分析的必要性。我们对五项研究中的 424 个大脑样本进行了荟萃分析，以确定影响人类皮质基因表达的调控变异。我们在常染色体和X染色体中鉴定出3584个基因，错误发现率q<0.05，其表达与DNA序列变异显着相关。与之前的 eQTL 研究一致，局部调控变异倾向于在转录起始位点周围对称发生，并且在大样本量的研究中效果更加明显。与随机 SNP 相比，我们观察到显着的 eQTL 更有可能位于 5'-非翻译区域附近并与调控特征相交叉。基于排列的富集分析显示，与精神分裂症和双相情感障碍相关的 SNP 在大脑 eQTL 中富集。具有显着 eQTL 证据的基因也与 OMIM（人类在线孟德尔遗传）和 NHGRI（国家人类基因组研究所）全基因组关联研究目录中的疾病密切相关。令人惊讶的是，我们发现大约 1000 个编码线粒体结构或功能所需蛋白质的常染色体基因中很大一部分 (28%) 是 eQTL（富集 P 值 = 1.3 × 10−9），这表明常见遗传变异可能影响大脑能量供应的稳健性，并且可能在某些精神疾病的病因学中发挥作用。这些系统生成的 eQTL 信息应该是确定大脑基因表达的功能机制以及与精神疾病相关的潜在生物学的宝贵资源。
Current catalogs of brain expression quantitative trait loci (eQTL) are incomplete and the findings do not replicate well across studies. All existing cortical eQTL studies are small and emphasize the need for a meta-analysis. We performed a meta-analysis of 424 brain samples across five studies to identify regulatory variants influencing gene expression in human cortex. We identified 3584 genes in autosomes and chromosome X with false discovery rate q<0.05 whose expression was significantly associated with DNA sequence variation. Consistent with previous eQTL studies, local regulatory variants tended to occur symmetrically around transcription start sites and the effect was more evident in studies with large sample sizes. In contrast to random SNPs, we observed that significant eQTLs were more likely to be near 5'-untranslated regions and intersect with regulatory features. Permutation-based enrichment analysis revealed that SNPs associated with schizophrenia and bipolar disorder were enriched among brain eQTLs. Genes with significant eQTL evidence were also strongly associated with diseases from OMIM (Online Mendelian Inheritance in Man) and the NHGRI (National Human Genome Research Institute) genome-wide association study catalog. Surprisingly, we found that a large proportion (28%) of ~1000 autosomal genes encoding proteins needed for mitochondrial structure or function were eQTLs (enrichment P-value=1.3 × 10−9), suggesting a potential role for common genetic variation influencing the robustness of energy supply in brain and a possible role in the etiology of some psychiatric disorders. These systematically generated eQTL information should be a valuable resource in determining the functional mechanisms of brain gene expression and the underlying biology of associations with psychiatric disorders.
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G2CDB：认知数据库的基因。
影响因子：
14.9
作者：
Croning MD;Marshall MC;McLaren P;Armstrong JD;Grant SG
通讯作者：
Grant SG
影响因子：
--
作者：
Fisher, RA
通讯作者：
Fisher, RA
影响因子：
64.8
作者：
Collins, Pamela Y.;Patel, Vikram;Joestl, Sarah S.;March, Dana;Insel, Thomas R.;Daar, Abdallah S.
通讯作者：
Daar, Abdallah S.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
5.6
作者：
Bassani, Silvia;Zapata, Jonathan;Passafaro, Maria
通讯作者：
Passafaro, Maria