Mapping of hepatic expression quantitative trait loci (eQTLs) in a Han Chinese population.
Mapping of hepatic expression quantitative trait loci (eQTLs) in a Han Chinese population.
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中国汉族人群肝脏表达数量性状位点 (eQTL) 的定位。
DOI：
10.1136/jmedgenet-2013-102045
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发表时间：
2014-05
影响因子：
4
通讯作者：
Peng Z
中科院分区：
文献类型：
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作者：
Wang X;Tang H;Teng M;Li Z;Li J;Fan J;Zhong L;Sun X;Xu J;Chen G;Chen D;Wang Z;Xing T;Zhang J;Huang L;Wang S;Peng X;Qin S;Shi Y;Peng Z
阐明肝脏基因表达变异性的遗传基础对了解该病的病因和药物代谢变化具有重要意义。迄今为止，还没有对世界上最大的民族汉族人群进行全基因组表达数量性状位点（eqtl）分析。我们对一组汉族肝脏组织样本（n=64）进行了全基因组eQTL定位。然后将这些数据与已发表的来自高加索人群的eQTL数据进行比较。然后，我们在这些eqtl与重要的药物基因之间进行了相关性研究，并通过全基因组关联研究（GWAS）鉴定了单核苷酸多态性（snp），特别是在亚洲人群中发现的单核苷酸多态性。我们的分析发现了1669个显著的eqtl（错误发现率(FDR) < 0.05）。我们发现41%的亚洲人的eqtl在全基因组显著性水平上与高加索人的eqtl相同（p=10−8）。亚洲人群中的顺式和反式eqtl也更有可能是白种人中的eqtl （p<10−4）。富集分析显示，性状相关的GWAS-SNPs在我们的数据中鉴定的eqtl中富集，在单独的分析中，亚洲人群中特异性鉴定的GWAS-SNPs也是如此（两者的p<0.001）。我们还发现，非常重要的药物遗传基因（VIP）的肝脏表达（n=44）和人工筛选的与药代动力学相关的主要基因列表（n=341）都更可能受到eqtl的控制（两者的p<0.002）。我们的研究首次在非欧洲人群中提供了全面的肝脏eQTL分析，进一步为表征人类疾病和药物遗传性状的遗传基础提供了有价值的数据。
Elucidating the genetic basis underlying hepatic gene expression variability is of importance to understand the aetiology of the disease and variation in drug metabolism. To date, no genome-wide expression quantitative trait loci (eQTLs) analysis has been conducted in the Han Chinese population, the largest ethnic group in the world. We performed a genome-wide eQTL mapping in a set of Han Chinese liver tissue samples (n=64). The data were then compared with published eQTL data from a Caucasian population. We then performed correlations between these eQTLs with important pharmacogenes, and genome-wide association study (GWAS) identified single nucleotide polymorphisms (SNPs), in particular those identified in the Asian population. Our analyses identified 1669 significant eQTLs (false discovery rate (FDR) < 0.05). We found that 41% of Asian eQTLs were also eQTLs in Caucasians at the genome-wide significance level (p=10−8). Both cis- and trans-eQTLs in the Asian population were also more likely to be eQTLs in Caucasians (p<10−4). Enrichment analyses revealed that trait-associated GWAS-SNPs were enriched within the eQTLs identified in our data, so were the GWAS-SNPs specifically identified in Asian populations in a separate analysis (p<0.001 for both). We also found that hepatic expression of very important pharmacogenetic (VIP) genes (n=44) and a manually curated list of major genes involved in pharmacokinetics (n=341) were both more likely to be controlled by eQTLs (p<0.002 for both). Our study provided, for the first time, a comprehensive hepatic eQTL analysis in a non-European population, further generating valuable data for characterising the genetic basis of human diseases and pharmacogenetic traits.
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DOI：
10.1097/00008571-199906000-00009
发表时间：
1999-06-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Lampe, JW;Bigler, J;Potter, JD
通讯作者：
Potter, JD
影响因子：
3.6
作者：
Hines, Ronald N.
通讯作者：
Hines, Ronald N.
影响因子：
4.5
作者：
Innocenti F;Cooper GM;Stanaway IB;Gamazon ER;Smith JD;Mirkov S;Ramirez J;Liu W;Lin YS;Moloney C;Aldred SF;Trinklein ND;Schuetz E;Nickerson DA;Thummel KE;Rieder MJ;Rettie AE;Ratain MJ;Cox NJ;Brown CD
通讯作者：
Brown CD
影响因子：
15.8
作者：
Brooks PJ;Enoch MA;Goldman D;Li TK;Yokoyama A
通讯作者：
Yokoyama A
影响因子：
30.8
作者：
通讯作者：
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