Integration of GWAS SNPs and tissue specific expression profiling reveal discrete eQTLs for human traits in blood and brain.
Integration of GWAS SNPs and tissue specific expression profiling reveal discrete eQTLs for human traits in blood and brain.
复制标题
DOI：
10.1016/j.nbd.2012.03.020
复制
发表时间：
2012-07
影响因子：
6.1
通讯作者：
Cookson MR
中科院分区：
文献类型：
--
作者：
Hernandez DG;Nalls MA;Moore M;Chong S;Dillman A;Trabzuni D;Gibbs JR;Ryten M;Arepalli S;Weale ME;Zonderman AB;Troncoso J;O'Brien R;Walker R;Smith C;Bandinelli S;Traynor BJ;Hardy J;Singleton AB;Cookson MR
全基因组关联研究已经为包括疾病在内的常见人类性状提名了许多遗传变异，但在许多情况下，性状关联的潜在生物学原因是未知的。遗传多态性的子集显示与转录本表达水平的统计学关联，并且因此被提名为表达数量性状基因座（eQTL）。然而，许多组织和细胞类型具有特定的基因表达模式，因此尚不清楚在一种组织类型中发现的eQTL在其他组织类型中复制的频率。在本研究中，我们使用了两个适当的动力样本系列来检查血液和大脑中基因表达的遗传控制。我们发现，虽然这两种组织之间共享许多与人类性状相关的eQTL，但也有血液和大脑不同的例子，无论是通过一种组织中的限制性基因表达模式，还是因为遗传变异与转录水平相关的差异。这些观察结果表明，eQTL定位实验的设计应考虑感兴趣的组织的疾病或其他性状的研究。我们整合了GWAS SNP，并检查了血液和脑组织中基因表达的遗传控制。许多与人类性状相关的eQTL在血液和大脑之间共享。许多离散的组织特异性eQTL也存在于血液或大脑中。血液中的功能研究在提供大脑调节变化方面的能力有限。eQTL定位实验的设计应考虑所研究表型的感兴趣组织。
Genome-wide association studies have nominated many genetic variants for common human traits, including diseases, but in many cases the underlying biological reason for a trait association is unknown. Subsets of genetic polymorphisms show a statistical association with transcript expression levels, and have therefore been nominated as expression quantitative trait loci (eQTL). However, many tissue and cell types have specific gene expression patterns and so it is not clear how frequently eQTLs found in one tissue type will be replicated in others. In the present study we used two appropriately powered sample series to examine the genetic control of gene expression in blood and brain. We find that while many eQTLs associated with human traits are shared between these two tissues, there are also examples where blood and brain differ, either by restricted gene expression patterns in one tissue or because of differences in how genetic variants are associated with transcript levels. These observations suggest that design of eQTL mapping experiments should consider tissue of interest for the disease or other traits studied. ► We integrate GWAS SNPs and examine the genetic control of gene expression in blood and brain tissue. ► Many eQTLs associated with human traits are shared between the blood and the brain. ► A number of discrete, tissue specific eQTLs also exist in the blood or the brain. ► Functional studies in blood have a limited capacity to inform on regulatory variation in the brain. ► Design of eQTL mapping experiments should consider the tissue of interest for the phenotype studied.