Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Jul;131(7):1225-34.
doi: 10.1007/s00439-012-1148-4. Epub 2012 Feb 26.

Genome-wide two-locus epistasis scans in prostate cancer using two European populations

Sha Tao  1 , Junjie Feng, Timothy Webster, Guangfu Jin, Fang-Chi Hsu, Shyh-Huei Chen, Seong-Tae Kim, Zhong Wang, Zheng Zhang, Siqun L Zheng, William B Isaacs, Jianfeng Xu, Jielin Sun
Affiliations

Genome-wide two-locus epistasis scans in prostate cancer using two European populations

Sha Tao et al. Hum Genet. 2012 Jul.

Abstract

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 (P(interaction) <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 P(interaction) 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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Interaction between rs7514217 and rs7934426 in CGEMS (a) and JHH (b). X axis represent the genotype for rs7514217, Y axis represent the genotype for rs7934426, the Z axis showed the odds ratio of the SNP pair (rs7514217 and rs7934426). Odds ratios are estimated relative to the baseline AA/AA double homozygote
Fig. 2
Fig. 2
Interaction between rs11980379 and rs4314028 in CGEMS (a) and JHH (b). X axis represent the genotype for rs11980379, Y axis represent the genotype for rs4314028 and the Z axis showed the odds ratio of the SNP pair (rs11980379 and rs4314028). Odds ratios are estimated relative to the baseline AA/AA double homozygote
See this image and copyright information in PMC

References

    1. Agresti A. Wiley Series in Probability and Statistics. 2nd edn. New York: Wiley; 2002. Categorical data analysis.
    1. Amundadottir LT, Sulem P, Gudmundsson J, Helgason A, Baker A, Agnarsson BA, Sigurdsson A, Benediktsdottir KR, Cazier JB, Sainz J, Jakobsdottir M, Kostic J, Magnusdottir DN, Ghosh S, Agnarsson K, Birgisdottir B, Le Roux L, Olafsdottir A, Blondal T, Andresdottir M, Gretarsdottir OS, Bergthorsson JT, Gudbjartsson D, Gylfason A, Thorleifsson G, Manolescu A, Kristjansson K, Geirsson G, Isaksson H, Douglas J, Johansson JE, Balter K, Wiklund F, Montie JE, Yu X, Suarez BK, Ober C, Cooney KA, Gronberg H, Catalona WJ, Einarsson GV, Barkardottir RB, Gulcher JR, Kong A, Thorsteinsdottir U, Stefansson K. A common variant associated with prostate cancer in European and African populations. Nat Genet. 2006;38:652–658. - PubMed
    1. Bateson W, Mendel G. Mendel’s principles of heredity. Cambridge: Cambridge University Press; 1909.
    1. Bell JT, Timpson NJ, Rayner NW, Zeggini E, Frayling TM, Hattersley AT, Morris AP, McCarthy MI. Genome-wide association scan allowing for epistasis in type 2 diabetes. Ann Hum Genet. 2011;75:10–19. - PMC - PubMed
    1. Carroll JS, Meyer CA, Song J, Li W, Geistlinger TR, Eeckhoute J, Brodsky AS, Keeton EK, Fertuck KC, Hall GF, Wang Q, Bekiranov S, Sementchenko V, Fox EA, Silver PA, Gingeras TR, Liu XS, Brown M. Genome-wide analysis of estrogen receptor binding sites. Nat Genet. 2006;38:1289–1297. - PubMed

Publication types