A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia
A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia
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DOI：
10.1038/ng.2843
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发表时间：
2014-01-01
期刊：
影响因子：
30.8
通讯作者：
Houlston, Richard S.
中科院分区：
文献类型：
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作者：
Speedy, Helen E.;Di Bernardo, Maria Chiara;Houlston, Richard S.
慢性淋巴细胞白血病（CLL）的全基因组关联研究（GWAS）表明，常见的遗传变异有助于CLL的遗传风险。为了确定其他CLL易感基因座，我们进行了GWAS，并对已发表的GWAS进行了荟萃分析，共有1，739名CLL患者（病例）和5，199名对照，并在另外1，144例病例和3，151名对照中进行了验证。综合分析发现了定位于3q26.2的新易感基因座（rs10936599，P = 1.74 x 10（-9）），4q26（rs6858698，P = 3.07 x 10（-9））、6q25.2（IPCEF 1，rs2236256，P = 1.50 x 10（-10））和7q31.33（POT1，rs17246404，P = 3.40 x 10（-8））。此外，我们在5p15.33（CLPTM 1 L，rs31490，P = 1.72 x 10（-7））处发现了有希望的关联，并验证了最近报道的在5p15.33（TERT，rs 10069690，P = 1.12 x 10（-10））和8q22.3（rs 2511714，P = 2.90 x 10（-9））的推定关联。这些发现为CLL遗传易感性的遗传和生物学基础提供了进一步的见解。
Genome-wide association studies (GWAS) of chronic lymphocytic leukemia (CLL) have shown that common genetic variation contributes to the heritable risk of CLL. To identify additional CLL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1,739 individuals with CLL (cases) and 5,199 controls with validation in an additional 1,144 cases and 3,151 controls. A combined analysis identified new susceptibility loci mapping to 3q26.2 (rs10936599, P = 1.74 x 10(-9)), 4q26 (rs6858698, P = 3.07 x 10(-9)), 6q25.2 (IPCEF1, rs2236256, P = 1.50 x 10(-10)) and 7q31.33 (POT1, rs17246404, P = 3.40 x 10(-8)). Additionally, we identified a promising association at 5p15.33 (CLPTM1L, rs31490, P = 1.72 x 10(-7)) and validated recently reported putative associations at 5p15.33 (TERT, rs10069690, P = 1.12 x 10(-10)) and 8q22.3 (rs2511714, P = 2.90 x 10(-9)). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL.