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Nat Genet. 2014 Jan;46(1):56-60. doi: 10.1038/ng.2843. Epub 2013 Dec 1.

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

Author information

1
1] Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK. [2].
2
Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK.
3
Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.
4
Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK.
5
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
6
Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Hematology and Transplantation, Lund University, Lund, Sweden.
7
Unit of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
8
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
9
Medical Research Council Toxicology Unit, Leicester University, Leicester, UK.
10
Haemato-Oncology, Division of Molecular Pathology, Institute of Cancer Research, Sutton, Surrey, UK.
11
Haematological Sciences, Medical School, Newcastle University, Newcastle-upon-Tyne, UK.
12
Department of Haematology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK.
13
Department of Haematology, Queen Elizabeth Hospital, Gateshead, Newcastle-upon-Tyne, UK.
14
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
15
Department of Haematology, Hull Royal Infirmary, Hull, UK.
16
Hull York Medical School and University of Hull, Hull, UK.
17
Department of Haematology, Birmingham Heartlands Hospital, Birmingham, UK.
18
Department of Haematology, School of Medicine, Cardiff University, Cardiff, UK.
19
Cardiff and Vale National Health Service Trust, Heath Park, Cardiff, UK.

Abstract

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 × 10(-9)), 4q26 (rs6858698, P = 3.07 × 10(-9)), 6q25.2 (IPCEF1, rs2236256, P = 1.50 × 10(-10)) and 7q31.33 (POT1, rs17246404, P = 3.40 × 10(-8)). Additionally, we identified a promising association at 5p15.33 (CLPTM1L, rs31490, P = 1.72 × 10(-7)) and validated recently reported putative associations at 5p15.33 (TERT, rs10069690, P = 1.12 × 10(-10)) and 8q22.3 (rs2511714, P = 2.90 × 10(-9)). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL.

PMID:
24292274
DOI:
10.1038/ng.2843
[Indexed for MEDLINE]

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