A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia

被引:291
作者
Di Bernardo, Maria Chiara [1 ]
Crowther-Swanepoel, Dalemari [1 ]
Broderick, Peter [1 ]
Webb, Emily [1 ]
Sellick, Gabrielle [1 ]
Wild, Ruth [1 ]
Sullivan, Kate [1 ]
Vijayakrishnan, Jayaram [1 ]
Wang, Yufei [1 ]
Pittman, Alan M. [1 ]
Sunter, Nicola J. [2 ]
Hall, Andrew G. [2 ]
Dyer, Martin J. S. [3 ]
Matutes, Estella [4 ]
Dearden, Claire [4 ]
Mainou-Fowler, Tryfonia [5 ]
Jackson, Graham H. [6 ]
Summerfield, Geoffrey [7 ]
Harris, Robert J. [8 ]
Pettitt, Andrew R. [8 ]
Hillmen, Peter [9 ]
Allsup, David J. [10 ]
Bailey, James R. [11 ,12 ]
Pratt, Guy [13 ]
Pepper, Chris [14 ]
Fegan, Chris [15 ]
Allan, James M. [2 ]
Catovsky, Daniel [4 ]
Houlston, Richard S. [1 ]
机构
[1] Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
[2] Newcastle Univ, No Inst Canc Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[3] Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England
[4] Inst Canc Res, Sect Haematooncol, Sutton SM2 5NG, Surrey, England
[5] Newcastle Univ, Sch Med, Newcastle Upon Tyne, Tyne & Wear, England
[6] Royal Victoria Infirm, Dept Haematol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England
[7] Queen Elizabeth Hosp, Dept Haematol, Newcastle Upon Tyne NE9 6SX, Tyne & Wear, England
[8] Univ Liverpool, Sch Canc Studies, Div Haematol, Liverpool L69 3BX, Merseyside, England
[9] Gen Infirm, Dept Haematol, Leeds LS1 3EX, W Yorkshire, England
[10] Hull Royal Infirm, Dept Haematol, Kingston Upon Hull HU3 2JZ, N Humberside, England
[11] Hull York Med Sch, Kingston Upon Hull HU16 5JQ, N Humberside, England
[12] Univ Hull, Kingston Upon Hull HU16 5JQ, N Humberside, England
[13] Birmingham Heartlands Hosp, Dept Haematol, Birmingham B9, W Midlands, England
[14] Cardiff Univ, Sch Med, Dept Haematol, Cardiff, S Glam, Wales
[15] Cardiff & Vale NHS Trust, Cardiff CF14 4XW, S Glam, Wales
基金
英国医学研究理事会;
关键词
D O I
10.1038/ng.219
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We conducted a genome-wide association study of 299,983 tagging SNPs for chronic lymphocytic leukemia (CLL) and performed validation in two additional series totaling 1,529 cases and 3,115 controls. We identified six previously unreported CLL risk loci at 2q13 (rs17483466; P = 2.36 x 10(-10)), 2q37.1 (rs13397985, SP140; P = 5.40 x 10(-10)), 6p25.3 (rs872071, IRF4; P = 1.91 x 10(-20)), 11q24.1 (rs735665; P = 3.78 x 10(-12)), 15q23 (rs7176508; P = 4.54 x 10(-12)) and 19q13.32 (rs11083846, PRKD2; P = 3.96 x 10(-9)). These data provide the first evidence for the existence of common, low-penetrance susceptibility to a hematological malignancy and new insights into disease causation in CLL.
引用
收藏
页码:1204 / 1210
页数:7
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