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

被引：161

作者：

Speedy, Helen E. ^{[1
]}

Di Bernardo, Maria Chiara ^{[1
]}

Sava, Georgina P. ^{[1
]}

Dyer, Martin J. S. ^{[2
]}

Holroyd, Amy ^{[1
]}

Wang, Yufei ^{[1
]}

Sunter, Nicola J. ^{[3
]}

Mansouri, Larry ^{[4
]}

Juliusson, Gunnar ^{[5
]}

Smedby, Karin E. ^{[6
]}

Roos, Groan ^{[7
]}

Jayne, Sandrine ^{[8
]}

Majid, Aneela ^{[8
]}

Dearden, Claire ^{[9
]}

Hall, Andrew G. ^{[3
]}

Mainou-Fowler, Tryfonia ^{[10
]}

Jackson, Graham H. ^{[11
]}

Summerfield, Geoffrey ^{[12
]}

Harris, Robert J. ^{[13
]}

Pettitt, Andrew R. ^{[13
]}

Allsup, David J. ^{[14
]}

Bailey, James R. ^{[15
,16
]}

Pratt, Guy ^{[17
]}

Pepper, Chris ^{[18
]}

Fegan, Chris ^{[19
]}

Rosenquist, Richard ^{[4
]}

Catovsky, Daniel ^{[9
]}

Allan, James M. ^{[3
]}

Houlston, Richard S. ^{[1
]}

机构：

[1] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England

[2] Univ Leicester, Dept Canc Studies & Mol Med, Leicester, Leics, England

[3] Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[4] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden

[5] Lund Univ, Lund Strateg Res Ctr Stem Cell Biol & Cell Therap, Lund, Sweden

[6] Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden

[7] Umea Univ, Dept Med Biosci Pathol, Umea, Sweden

[8] Univ Leicester, Toxicol Unit, Med Res Council, Leicester, Leics, England

[9] Inst Canc Res, Div Mol Pathol, Sutton, Surrey, England

[10] Newcastle Univ, Sch Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[11] Royal Victoria Infirm, Dept Haematol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England

[12] Queen Elizabeth Hosp, Dept Haematol, Newcastle Upon Tyne, Tyne & Wear, England

[13] Univ Liverpool, Dept Mol & Clin Canc Med, Liverpool L69 3BX, Merseyside, England

[14] Hull Royal Infirm, Dept Haematol, Kingston Upon Hull HU3 2JZ, N Humberside, England

[15] Hull York Med Sch, Kingston Upon Hull, N Humberside, England

[16] Univ Hull, Kingston Upon Hull HU6 7RX, N Humberside, England

[17] Birmingham Heartlands Hosp, Dept Haematol, Birmingham B9 5ST, W Midlands, England

[18] Cardiff Univ, Sch Med, Dept Haematol, Cardiff CF10 3AX, S Glam, Wales

[19] Cardiff & Vale Natl Hlth Serv Trust, Cardiff, S Glam, Wales

来源：

NATURE GENETICS | 2014年 / 46卷 / 01期

关键词：

COLORECTAL-CANCER; TELOMERE LENGTH; CHROMATIN STATES; COMMON VARIATION; CELL-RECEPTOR; LUNG-CANCER; RISK; VARIANTS; PCR; METAANALYSIS;

D O I：

10.1038/ng.2843

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：56 / +

页数：7

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