Genome-wide association study identifies novel loci predisposing to cutaneous melanoma
Genome-wide association study identifies novel loci predisposing to cutaneous melanoma
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DOI：
10.1093/hmg/ddr415
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发表时间：
2011-12-15
影响因子：
3.5
通讯作者：
Wei, Qingyi
中科院分区：
文献类型：
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作者：
Amos, Christopher I.;Wang, Li-E;Wei, Qingyi
我们进行了一项黑色素瘤的多阶段全基因组相关性研究。在发现的1804例黑色素瘤病例和1026例对照中，我们在染色体15q13.1(HERC2/OCA2区域)和16q24.3(MC1R)区域确定了在本研究中达到全基因组意义的基因座，并发现了位于染色体9p21.3上的p16/ARF区域和染色体1q21.3(Arnt/LASS2/ANXA9区域)上的标记对黑色素瘤易感性的强烈证据。15q13.1基因座最显著的单核苷酸多态(SNPs)(rs1129038和rs12913832)位于对眼睛和肤色有重大影响的基因组区域；值得注意的是，眼睛颜色的50%变异与SNP rs12913832的变异有关。由于眼睛和皮肤的颜色在欧洲人群中不同，我们在仔细调整欧洲人的亚结构后，进一步评估了显著的SNPs的相关性。我们还通过使用其他三个全基因组扫描的数据来评估前10个最重要的SNPs。此外，电子计算机数据提供了来自染色体1q21.3 rs7412746(P=6 x 10(-10))上最重要区域的发现的重复。总而言之，这些数据确定了几个候选基因，用于进一步研究，以确定易患黑色素瘤风险增加的因果变异。
We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 x 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.