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.

Figure 1

Regional association plots. (a,b) Regional plots (top) and LD maps (bottom) at 9q31.2 (a) and 19q13.4 (b). For regional plots, association of individual SNP is plotted as –log₁₀P against chromosomal position. Results for both genotyped and imputed SNPs are shown. Symbol colors represent the LD of the SNP with the most significant SNP at each locus (purple diamond). The right y axis shows the recombination rate estimated from 1000 Genomes Project CHB and JPT data. LD maps were based on D′ values using CHB and JPT genotypes from the 1000 Genomes Project (Phase 1 integrated data version 3, released March 2012).

Figure 2

Germline deletion at LILRA3 and genotyped SNPs flanking the gene. Top, schematic of the LILRA3 deletion that is in strong LD with prostate cancer risk–associated SNP rs103294 at 19q13.4. Bottom, pairwise LD (r²) values calculated based on data from GWAS stage samples.