Common genetic variation contributes significantly to the risk of childhood B-cell precursor acute lymphoblastic leukemia
Common genetic variation contributes significantly to the risk of childhood B-cell precursor acute lymphoblastic leukemia
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DOI：
10.1038/leu.2012.89
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发表时间：
2012-10-01
期刊：
影响因子：
11.4
通讯作者：
Houlston, R. S.
中科院分区：
文献类型：
--
作者：
Enciso-Mora, V.;Hosking, F. J.;Houlston, R. S.
最近的全基因组关联研究（GWAS）提供了第一个明确的证据，即常见的遗传变异影响儿童B细胞前体急性淋巴细胞白血病（BCP-ALL）的风险，确定了定位于7p12.2，9p21.3，10q21.2和14q11.2的风险单核苷酸多态性（SNP）。在GWA研究中单独测试SNP的关联需要施加非常严格的P值来解决多次测试的问题。虽然这减少了假阳性，但可能会错过真实的关联，因此对总遗传力的任何估计都将有负偏差。通过同时考虑所有类型的SNP，使用823例BCP-ALL病例的GWAS数据，我们计算出BCP-ALL风险的总变异的24%是常见的遗传变异（95%置信区间6-42%）。我们的研究结果为BCP-ALL易感性的多基因基础提供了支持，并对未来寻找新的致病风险变异具有更广泛的意义。白血病（2012）26，2212-2215; doi：10.1038/leu.2012.89
Recent genome-wide association studies (GWAS) have provided the first unambiguous evidence that common genetic variation influences the risk of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), identifying risk single-nucleotide polymorphisms (SNPs) localizing to 7p12.2, 9p21.3, 10q21.2 and 14q11.2. The testing of SNPs individually for an association in GWA studies necessitates the imposition of a very stringent P-value to address the issue of multiple testing. While this reduces false positives, real associations may be missed and therefore any estimate of the total heritability will be negatively biased. Using GWAS data on 823 BCP-ALL cases by considering all typed SNPs simultaneously, we have calculated that 24% of the total variation in BCP-ALL risk is accounted for common genetic variation (95% confidence interval 6-42%). Our findings provide support for a polygenic basis for susceptibility to BCP-ALL and have wider implications for future searches for novel disease-causing risk variants. Leukemia (2012) 26, 2212-2215; doi:10.1038/leu.2012.89