New aQTL SNPs for the CYP2D6 identified by a novel mediation analysis of genome-wide SNP arrays, gene expression arrays, and CYP2D6 activity.
New aQTL SNPs for the CYP2D6 identified by a novel mediation analysis of genome-wide SNP arrays, gene expression arrays, and CYP2D6 activity.
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DOI：
10.1155/2013/493019
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发表时间：
2013
影响因子：
--
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Jiang G;Chakraborty A;Wang Z;Boustani M;Liu Y;Skaar T;Li L
背景。全基因组关联研究（GWAS）在过去几年中取得了成功。一个关键的挑战是，对结果的解释并不直截了当，尤其是对snp的处理。将转录组数据整合到GWAS中可能为阐明遗传变异导致疾病的机制提供线索。方法。在这里，我们开发了一种新的中介分析方法，通过结合基因型、基因表达和酶活性数据来鉴定驱动CYP2D6活性的新的表达数量性状位点（eQTL）。结果：在Affymetrix和Illumina两种不同的基因型平台上，分别发现389,573和1,214,416个snp -转录- cyp2d6活性三组强相关（P < 10−5,FDR = 16.6%和11.7%）。大多数相等qtl是反式snp。单个多态性通过影响主要调控因子或转录因子（tf）导致远端基因表达的广泛下游变化，这将是一个可见的eQTL热点，并可能导致大而一致的生物效应。与介质重叠的eQTL热点导致64个tf的发现。结论。我们的中介分析是识别反式qtl表型关联的有力方法。它提高了我们对肝脏代谢机制的功能性遗传变异的理解。
Background. The genome-wide association studies (GWAS) have been successful during the last few years. A key challenge is that the interpretation of the results is not straightforward, especially for transacting SNPs. Integration of transcriptome data into GWAS may provide clues elucidating the mechanisms by which a genetic variant leads to a disease. Methods. Here, we developed a novel mediation analysis approach to identify new expression quantitative trait loci (eQTL) driving CYP2D6 activity by combining genotype, gene expression, and enzyme activity data. Results. 389,573 and 1,214,416 SNP-transcript-CYP2D6 activity trios are found strongly associated (P < 10−5, FDR = 16.6% and 11.7%) for two different genotype platforms, namely, Affymetrix and Illumina, respectively. The majority of eQTLs are trans-SNPs. A single polymorphism leads to widespread downstream changes in the expression of distant genes by affecting major regulators or transcription factors (TFs), which would be visible as an eQTL hotspot and can lead to large and consistent biological effects. Overlapped eQTL hotspots with the mediators lead to the discovery of 64 TFs. Conclusions. Our mediation analysis is a powerful approach in identifying the trans-QTL-phenotype associations. It improves our understanding of the functional genetic variations for the liver metabolism mechanisms.
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影响因子：
7.6
作者：
BARON, RM;KENNY, DA
通讯作者：
KENNY, DA
中国汉族人群细胞色素P450 2D6启动子多态性的系统功能研究。
影响因子：
3.7
作者：
Gong X;Liu Y;Zhang X;Wei Z;Huo R;Shen L;He L;Qin S
通讯作者：
Qin S
影响因子：
30.8
作者：
Goering, Harald H. H.;Curran, Joanne E.;Blangero, John
通讯作者：
Blangero, John
DOI：
10.1080/00949659908811936
发表时间：
1999-01-01
影响因子：
1.2
作者：
Anderson, MJ;Legendre, P
通讯作者：
Legendre, P
影响因子：
2
作者：
Bin, H;Sivaganesan, S;Goodman, E
通讯作者：
Goodman, E