Multilevel-analysis identify a cis-expression quantitative trait locus associated with risk of renal cell carcinoma

Xiang Shu; Mark P. Purdue; Yuanqing Ye; Christopher G. Wood; Meng Chen; Zhaoming Wang; Demetrius Albanes; Xia Pu; Maosheng Huang; Victoria L. Stevens; W. Ryan Diver; Susan M. Gapstur; Jarmo Virtamo; Wong Ho Chow; Nizar M. Tannir; Colin P. Dinney; Nathaniel Rothman; Stephen J. Chanock; Xifeng Wu

doi:10.18632/oncotarget.3001

Multilevel-analysis identify a cis-expression quantitative trait locus associated with risk of renal cell carcinoma

Xiang Shu, Mark P. Purdue, Yuanqing Ye, Christopher G. Wood, Meng Chen, Zhaoming Wang, Demetrius Albanes, Xia Pu, Maosheng Huang, Victoria L. Stevens, W. Ryan Diver, Susan M. Gapstur, Jarmo Virtamo, Wong Ho Chow, Nizar M. Tannir, Colin P. Dinney, Nathaniel Rothman, Stephen J. Chanock, Xifeng Wu

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1 Scopus citations

Abstract

We conducted multilevel analyses to identify potential susceptibility loci for renal cell carcinoma (RCC), which may be overlooked in traditional genome-wide association studies (GWAS). A gene set enrichment analysis was performed utilizing a GWAS dataset comprised of 894 RCC cases and 1,516 controls using GenGen, SNP ratio test, and ALIGATOR. The antigen processing and presentation pathway was consistently significant (P = 0.001, = 0.004, and < 0.001, respectively). Versatile gene-based association study approach was applied to the top-ranked pathway and identified the driven genes. By comparing the expression of the genes in RCC tumor and adjacent normal tissues, we observed significant overexpression of HLA genes in tumor tissues, which was also supported by public databases. We sought to validate genetic variants in antigen processing and presentation pathway in an independent GWAS dataset comprised of 1,311 RCC cases and 3,424 control subjects from the National Cancer Institute; one SNP, rs1063355, was significant in both populations (P_{meta-analysis} = 9.15 × 10^-4, P_{heterogeneity} = 0.427). Strong correlation indicated that rs1063355 was a cis-expression quantitative trait loci which associated with HLADQB1 expression (Spearman's rank r = -0.59, p = 5.61 × 10^-6). The correlation was further validated using a public dataset. Our results highlighted the role of immunerelated pathway and genes in the etiology of RCC.

Original language	English (US)
Pages (from-to)	4097-4109
Number of pages	13
Journal	Oncotarget
Volume	6
Issue number	6
DOIs	https://doi.org/10.18632/oncotarget.3001
State	Published - 2015

Keywords

EQTL
GSEA
GWAS
RCC

ASJC Scopus subject areas

Oncology

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Shu, X., Purdue, M. P., Ye, Y., Wood, C. G., Chen, M., Wang, Z., Albanes, D., Pu, X., Huang, M., Stevens, V. L., Ryan Diver, W., Gapstur, S. M., Virtamo, J., Chow, W. H., Tannir, N. M., Dinney, C. P., Rothman, N., Chanock, S. J., & Wu, X. (2015). Multilevel-analysis identify a cis-expression quantitative trait locus associated with risk of renal cell carcinoma. Oncotarget, 6(6), 4097-4109. https://doi.org/10.18632/oncotarget.3001

Shu, X, Purdue, MP, Ye, Y, Wood, CG, Chen, M, Wang, Z, Albanes, D, Pu, X, Huang, M, Stevens, VL, Ryan Diver, W, Gapstur, SM, Virtamo, J, Chow, WH, Tannir, NM , Dinney, CP, Rothman, N, Chanock, SJ & Wu, X 2015, 'Multilevel-analysis identify a cis-expression quantitative trait locus associated with risk of renal cell carcinoma', Oncotarget, vol. 6, no. 6, pp. 4097-4109. https://doi.org/10.18632/oncotarget.3001

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title = "Multilevel-analysis identify a cis-expression quantitative trait locus associated with risk of renal cell carcinoma",

abstract = "We conducted multilevel analyses to identify potential susceptibility loci for renal cell carcinoma (RCC), which may be overlooked in traditional genome-wide association studies (GWAS). A gene set enrichment analysis was performed utilizing a GWAS dataset comprised of 894 RCC cases and 1,516 controls using GenGen, SNP ratio test, and ALIGATOR. The antigen processing and presentation pathway was consistently significant (P = 0.001, = 0.004, and < 0.001, respectively). Versatile gene-based association study approach was applied to the top-ranked pathway and identified the driven genes. By comparing the expression of the genes in RCC tumor and adjacent normal tissues, we observed significant overexpression of HLA genes in tumor tissues, which was also supported by public databases. We sought to validate genetic variants in antigen processing and presentation pathway in an independent GWAS dataset comprised of 1,311 RCC cases and 3,424 control subjects from the National Cancer Institute; one SNP, rs1063355, was significant in both populations (Pmeta-analysis = 9.15 × 10-4, Pheterogeneity = 0.427). Strong correlation indicated that rs1063355 was a cis-expression quantitative trait loci which associated with HLADQB1 expression (Spearman's rank r = -0.59, p = 5.61 × 10-6). The correlation was further validated using a public dataset. Our results highlighted the role of immunerelated pathway and genes in the etiology of RCC.",

keywords = "EQTL, GSEA, GWAS, RCC",

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doi = "10.18632/oncotarget.3001",

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AU - Shu, Xiang

AU - Purdue, Mark P.

AU - Ye, Yuanqing

AU - Wood, Christopher G.

AU - Chen, Meng

AU - Wang, Zhaoming

AU - Albanes, Demetrius

AU - Pu, Xia

AU - Huang, Maosheng

AU - Stevens, Victoria L.

AU - Ryan Diver, W.

AU - Gapstur, Susan M.

AU - Virtamo, Jarmo

AU - Chow, Wong Ho

AU - Tannir, Nizar M.

AU - Dinney, Colin P.

AU - Rothman, Nathaniel

AU - Chanock, Stephen J.

AU - Wu, Xifeng

PY - 2015

Y1 - 2015

N2 - We conducted multilevel analyses to identify potential susceptibility loci for renal cell carcinoma (RCC), which may be overlooked in traditional genome-wide association studies (GWAS). A gene set enrichment analysis was performed utilizing a GWAS dataset comprised of 894 RCC cases and 1,516 controls using GenGen, SNP ratio test, and ALIGATOR. The antigen processing and presentation pathway was consistently significant (P = 0.001, = 0.004, and < 0.001, respectively). Versatile gene-based association study approach was applied to the top-ranked pathway and identified the driven genes. By comparing the expression of the genes in RCC tumor and adjacent normal tissues, we observed significant overexpression of HLA genes in tumor tissues, which was also supported by public databases. We sought to validate genetic variants in antigen processing and presentation pathway in an independent GWAS dataset comprised of 1,311 RCC cases and 3,424 control subjects from the National Cancer Institute; one SNP, rs1063355, was significant in both populations (Pmeta-analysis = 9.15 × 10-4, Pheterogeneity = 0.427). Strong correlation indicated that rs1063355 was a cis-expression quantitative trait loci which associated with HLADQB1 expression (Spearman's rank r = -0.59, p = 5.61 × 10-6). The correlation was further validated using a public dataset. Our results highlighted the role of immunerelated pathway and genes in the etiology of RCC.

AB - We conducted multilevel analyses to identify potential susceptibility loci for renal cell carcinoma (RCC), which may be overlooked in traditional genome-wide association studies (GWAS). A gene set enrichment analysis was performed utilizing a GWAS dataset comprised of 894 RCC cases and 1,516 controls using GenGen, SNP ratio test, and ALIGATOR. The antigen processing and presentation pathway was consistently significant (P = 0.001, = 0.004, and < 0.001, respectively). Versatile gene-based association study approach was applied to the top-ranked pathway and identified the driven genes. By comparing the expression of the genes in RCC tumor and adjacent normal tissues, we observed significant overexpression of HLA genes in tumor tissues, which was also supported by public databases. We sought to validate genetic variants in antigen processing and presentation pathway in an independent GWAS dataset comprised of 1,311 RCC cases and 3,424 control subjects from the National Cancer Institute; one SNP, rs1063355, was significant in both populations (Pmeta-analysis = 9.15 × 10-4, Pheterogeneity = 0.427). Strong correlation indicated that rs1063355 was a cis-expression quantitative trait loci which associated with HLADQB1 expression (Spearman's rank r = -0.59, p = 5.61 × 10-6). The correlation was further validated using a public dataset. Our results highlighted the role of immunerelated pathway and genes in the etiology of RCC.

KW - EQTL

KW - GSEA

KW - GWAS

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JO - Oncotarget

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Multilevel-analysis identify a cis-expression quantitative trait locus associated with risk of renal cell carcinoma

Abstract

Keywords

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