Characterisation of genome-wide association epistasis signals for serum uric acid in human population isolates.
Characterisation of genome-wide association epistasis signals for serum uric acid in human population isolates.
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DOI：
10.1371/journal.pone.0023836
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Haley CS
中科院分区：
文献类型：
--
作者：
Wei W;Hemani G;Hicks AA;Vitart V;Cabrera-Cardenas C;Navarro P;Huffman J;Hayward C;Knott SA;Rudan I;Pramstaller PP;Wild SH;Wilson JF;Campbell H;Dunlop MG;Hastie N;Wright AF;Haley CS
全基因组关联（GWA）研究已经确定了许多基因座潜在的人类血清尿酸（SUA）水平的变化，SLC 2A 9基因具有迄今为止确定的最大影响。基因-基因相互作用（上位性）在这些GWA研究中基本上未被探索。我们在意大利MICROS群体（n = 1201）中进行了全成对基因组扫描，以在SUA水平上检测上位性信号。 在所得上位性谱中，没有SNP对达到用于成对全基因组显著性的Bonferroni调整阈值。然而，发现SLC 2A 9与整个基因组中的多个基因座相互作用，根据GWA显着SNP与基因组之间相互作用推导出的阈值，NFIA -SLC 2A 9和SLC 2A 9-ESRRAP 2具有显着性，并共同解释了8.0%的SUA水平表型变异（3.4%由相互作用成分决定）。上位性信号复制在克罗地亚人口（n = 1772）是有限的SNP水平，但在基因本体水平显着改善。 此外，基因本体论术语丰富的上位性信号在每个人口支持SUA水平和神经系统疾病之间的联系。我们的结论是，GWA上位性分析是有用的，尽管相对较低的功率在小的孤立的人群。
Genome-wide association (GWA) studies have identified a number of loci underlying variation in human serum uric acid (SUA) levels with the SLC2A9 gene having the largest effect identified so far. Gene-gene interactions (epistasis) are largely unexplored in these GWA studies. We performed a full pair-wise genome scan in the Italian MICROS population (n = 1201) to characterise epistasis signals in SUA levels. In the resultant epistasis profile, no SNP pairs reached the Bonferroni adjusted threshold for the pair-wise genome-wide significance. However, SLC2A9 was found interacting with multiple loci across the genome, with NFIA - SLC2A9 and SLC2A9 - ESRRAP2 being significant based on a threshold derived for interactions between GWA significant SNPs and the genome and jointly explaining 8.0% of the phenotypic variance in SUA levels (3.4% by interaction components). Epistasis signal replication in a CROATIAN population (n = 1772) was limited at the SNP level but improved dramatically at the gene ontology level. In addition, gene ontology terms enriched by the epistasis signals in each population support links between SUA levels and neurological disorders. We conclude that GWA epistasis analysis is useful despite relatively low power in small isolated populations.
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影响因子：
16.2
作者：
Brandstätter A;Kiechl S;Kollerits B;Hunt SC;Heid IM;Coassin S;Willeit J;Adams TD;Illig T;Hopkins PN;Kronenberg F
通讯作者：
Kronenberg F
影响因子：
3.1
作者：
Facheris, Maurizio F.;Hicks, Andrew A.;Pramstaller, Peter P.
通讯作者：
Pramstaller, Peter P.
影响因子：
5
作者：
Gauderman, WJ
通讯作者：
Gauderman, WJ
DOI：
10.1073/pnas.0903103106
发表时间：
2009-06-09
影响因子：
11.1
作者：
Hindorff, Lucia A.;Sethupathy, Praveen;Manolio, Teri A.
通讯作者：
Manolio, Teri A.
影响因子：
16.2
作者：
Dehghan, Abbas;van Hoek, Mandy;Witteman, Jacqueline C. M.
通讯作者：
Witteman, Jacqueline C. M.