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Fine mapping analysis of a region of 20q13.33 identified five independent susceptibility loci for glioma in a Chinese Han population.

Genome-wide association studies have identified the susceptibility single nucleotide polymorphisms (SNPs) of glioma at chromosome 20q13.33, and the replication study conducted among Chinese Han population also confirmed the susceptibility locus rs6010620 is located in this region. To identify other genetic variants in 20q13.33, we genotyped 13 common tagging SNPs and imputed 86 additional SNPs in a region ∼100 kb at 20q13.33 among 1027 controls and 987 cases. Among 99 SNPs, five independent susceptibility loci (20-62315594 in RTEL1, 20-62335293 in adenosine diphosphate ribosylation factor-related protein 1, rs3761121 in ZGPAT, rs1058319 in SLC2A4RG and rs5019252 in ZBTB46) were identified for glioma. Two of the five SNPs (20-62335293, P = 3.09 × 10(-10) and rs1058319, P = 1.26 × 10(-11)) satisfied the threshold of genome-wide significance (P < 10(-8)). Further stratified analysis revealed that 20-62315594 was only significantly associated with glioblastoma (GBM) risk [P = 1.71 × 10(-8) for trend test, adjusted odds ratio (OR) = 1.99, 95% confidence interval (CI) = 1.57-2.52]. Other four SNPs were significantly associated with both GBM and astrocytoma. The risk of glioma increased with the increase of the number of risk alleles (P = 1.94 × 10(-11), for trend test, adjusted OR = 1.43, 95% CI = 1.29-1.58), and the individuals who carried 7-10 risk alleles had a 2.64-fold increased risk of glioma development compared with those who carried 0 risk allele (P = 8.71 × 10(-7), adjusted OR = 2.64, 95% CI = 1.79-3.88). Our results indicated a complex effect contributing to glioma risk at 20q13.33, which may provide a new insight into glioma development. Both variants and genes in this region should be considered in future studies designed to investigate the biological functions.