Genome-wide two-locus epistasis scans in prostate cancer using two European populations.
Genome-wide two-locus epistasis scans in prostate cancer using two European populations.
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DOI：
10.1007/s00439-012-1148-4
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发表时间：
2012-07
期刊：
影响因子：
5.3
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Tao S;Feng J;Webster T;Jin G;Hsu FC;Chen SH;Kim ST;Wang Z;Zhang Z;Zheng SL;Isaacs WB;Xu J;Sun J
通过全基因组关联研究（GWAS）发现了大约40个与前列腺癌（PCa）风险相关的单核苷酸多态性（snp）。然而，这些gwas鉴定的PCa风险相关snp只能解释一小部分PCa风险的遗传性（约13%）。据推测，基因间的相互作用是导致所谓的遗传性缺失的主要因素之一。为了评估基因-基因相互作用和PCa风险，我们使用一种名为“布尔运算筛选和测试”的新型统计方法进行了两阶段全基因组基因-基因相互作用扫描。在第一阶段，我们详尽地评估了来自国家癌症研究所癌症遗传易感性标记（CGEMS）研究的1176例PCa病例和1101例对照受试者中约500,000个SNP-SNP相互作用的所有对。没有SNP-SNP相互作用达到4.4E-13的全基因组显著水平。研究的第二阶段包括评估来自约翰霍普金斯医院（JHH）的1964例PCa患者和来自Illumina iControl数据库的3172例对照患者的另一个GWAS人群中涉及CGEMS的前1325对SNP-SNP相互作用（p相互作用< 1.0E-08）。在JHH人群中，有16对SNP-SNP互作显著，p互作截断值为0.01。然而，经过多次测试调整后，16对SNP-SNP相互作用均不显著。目前的研究是在全基因组范围内探索PCa高维病因学的首次尝试之一。我们的结果提出了一系列SNP-SNP相互作用，可以在其他复制研究中遵循。
Approximately 40 single nucleotide polymorphisms (SNPs) that are associated with prostate cancer (PCa) risk have been identified through genome-wide association studies (GWAS). However, these GWAS-identified PCa risk-associated SNPs can explain only a small proportion of heritability (~13%) of PCa risk. Gene–gene interaction is speculated to be one of the major factors contributing to the so-called missing heritability. To evaluate the gene–gene interaction and PCa risk, we performed a two-stage genome-wide gene–gene interaction scan using a novel statistical approach named “Boolean Operation-based Screening and Testing”. In the first stage, we exhaustively evaluated all pairs of SNP–SNP interactions for ~500,000 SNPs in 1,176 PCa cases and 1,101 control subjects from the National Cancer Institute Cancer Genetic Markers of Susceptibility (CGEMS) study. No SNP–SNP interaction reached a genome-wide significant level of 4.4E–13. The second stage of the study involved evaluation of the top 1,325 pairs of SNP–SNP interactions (Pinteraction < 1.0E–08) implicated in CGEMS in another GWAS population of 1,964 PCa cases from the Johns Hopkins Hospital (JHH) and 3,172 control subjects from the Illumina iControl database. Sixteen pairs of SNP–SNP interactions were significant in the JHH population at a Pinteraction cutoff of 0.01. However, none of the 16 pairs of SNP–SNP interactions were significant after adjusting for multiple tests. The current study represents one of the first attempts to explore the high-dimensional etiology of PCa on a genome-wide scale. Our results suggested a list of SNP–SNP interactions that can be followed in other replication studies.
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DOI：
10.1038/nrg2579
发表时间：
2009-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Cordell HJ
通讯作者：
Cordell HJ
影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
多阶段全基因组关联研究确定了七个前列腺癌易感位点
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Carroll, Jason S.;Meyer, Clifford A.;Brown, Myles
通讯作者：
Brown, Myles
影响因子：
11.2
作者：
Hsu FC;Sun J;Wiklund F;Isaacs SD;Wiley KE;Purcell LD;Gao Z;Stattin P;Zhu Y;Kim ST;Zhang Z;Liu W;Chang BL;Walsh PC;Duggan D;Carpten JD;Isaacs WB;Grönberg H;Xu J;Zheng SL
通讯作者：
Zheng SL