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Genome-wide association study in Chinese men identifies two new prostate cancer risk loci at 9q31.2 and 19q13.4

Abstract

Prostate cancer risk–associated variants have been reported in populations of European descent, African-Americans and Japanese using genome-wide association studies (GWAS). To systematically investigate prostate cancer risk–associated variants in Chinese men, we performed the first GWAS in Han Chinese. In addition to confirming several associations reported in other ancestry groups, this study identified two new risk-associated loci for prostate cancer on chromosomes 9q31.2 (rs817826, P = 5.45 × 10−14) and 19q13.4 (rs103294, P = 5.34 × 10−16) in 4,484 prostate cancer cases and 8,934 controls. The rs103294 marker at 19q13.4 is in strong linkage equilibrium with a 6.7-kb germline deletion that removes the first six of seven exons in LILRA3, a gene regulating inflammatory response, and was significantly associated with the mRNA expression of LILRA3 in T cells (P < 1 × 10−4). These findings may advance the understanding of genetic susceptibility to prostate cancer.

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Figure 1: Regional association plots.
Figure 2: Germline deletion at LILRA3 and genotyped SNPs flanking the gene.

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Acknowledgements

We thank all of the subjects included in this study. This work was partially funded by the National Key Basic Research Program grant 973 (2012CB518300 to Y.S and 2012CB518301 to J.X.), the Key Project of the National Natural Science Foundation of China (81130047 to J.X.), intramural grants from the Fudan University Thousand Talents Program and Huashan Hospital (to J.X.), the US National Institutes of Health (NCI CA129684 to J.X.), the National Natural Science Foundation of China (30945204 to Z.M and 30973009 to D.Y.), the Ministry of Health Special Research Fund for Public Interests (201002007 to L.J.) and the National Science & Technology Pillar Program (2011BAI09B00 to L.J.).

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Authors

Contributions

Y.S., J.X. and Z.M. directed the study, obtained financial support and were responsible for study design, interpretation of results and manuscript writing. D.Y., M.W., F.L. and C.X. recruited study subjects and managed respective project. G.J. performed statistical analyses, summarized results and drafted the manuscript. X.W., Q.S., Z.C., Z.T., J.Q., F.Z., Zhong Wang (affiliation 20), Y.F., D.H., Q. Wei, J. Guo, D.W., Xin Gao, J. Yuan, Gongxian Wang, Y. Xu, Guozeng Wang, H. Yao, P.D., Y.J., M.S., J. Yang, J.O.-Y., H.J., Y. Zhu, S.R., Z.Z., C.Y., Xu Gao, B.D., Z.H., Y.Y., Q. Wu, H.C., P.P., Y. Zheng, X. Zheng, Y. Xiang, J. Gong, R.N. and X.L. recruited subjects and prepared samples. J.L., X.-O.S., W.Z. and X. Zhang provided the allele frequency data from their GWAS populations. H. Yu, Zhong Wang (affiliation 4), S.T., J.F., Jishan Sun and W.L. performed statistical and bioinformatics analyses and carried out experiments. F.W. and H.G. provided samples and information from CAPS. A.H., J.R., Q.D., H.S., L.J., R.S., D.L., Jielin Sun and S.L.Z. coordinated the project. All of the authors reviewed, approved and contributed to the final version of the manuscript.

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Correspondence to Yinghao Sun.

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The authors declare no competing financial interests.

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Xu, J., Mo, Z., Ye, D. et al. Genome-wide association study in Chinese men identifies two new prostate cancer risk loci at 9q31.2 and 19q13.4. Nat Genet 44, 1231–1235 (2012). https://doi.org/10.1038/ng.2424

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