Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1
Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1
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DOI：
10.1038/ng.109
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发表时间：
2008-05-01
期刊：
影响因子：
30.8
通讯作者：
Houlston, Richard S.
中科院分区：
文献类型：
--
作者：
Amos, Christopher I.;Wu, Xifeng;Houlston, Richard S.
为了确定肺癌的风险变异，我们进行了多阶段全基因组关联研究。在发现阶段，我们分析了来自德克萨斯州休斯顿的1，154例当前和以前（曾经）吸烟的欧洲血统病例和1，137例频率匹配的吸烟对照中的315，450个标签SNP。为了重复，我们在德克萨斯州的另外711例病例和632例对照以及英国的2，013例病例和3，062例对照中评估了与肺癌最显著相关的10个SNP。两个SNPs，rs 1051730和rs 8034191，映射到15q25.1内含有PSMA 4和烟碱乙酰胆碱受体亚基基因CHRNA 3和CHRNA 5的强连锁不平衡区域，与两个复制集的风险显著相关。联合分析得出两种SNP的优势比为1.32（P < 1 x 10（-17））。单倍型分析与该区域存在单一风险变异一致。我们的结论是，在15q25.1区域的变异含有烟碱乙酰胆碱受体基因有助于肺癌的风险。
To identify risk variants for lung cancer, we conducted a multistage genome-wide association study. In the discovery phase, we analyzed 315,450 tagging SNPs in 1,154 current and former (ever) smoking cases of European ancestry and 1,137 frequency-matched, ever-smoking controls from Houston, Texas. For replication, we evaluated the ten SNPs most significantly associated with lung cancer in an additional 711 cases and 632 controls from Texas and 2,013 cases and 3,062 controls from the UK. Two SNPs, rs1051730 and rs8034191, mapping to a region of strong linkage disequilibrium within 15q25.1 containing PSMA4 and the nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5, were significantly associated with risk in both replication sets. Combined analysis yielded odds ratios of 1.32 (P < 1 x 10(-17)) for both SNPs. Haplotype analysis was consistent with there being a single risk variant in this region. We conclude that variation in a region of 15q25.1 containing nicotinic acetylcholine receptors genes contributes to lung cancer risk.