title: A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.
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.
authors.affiliation: 1] Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK. [2].
authors.forename: Helen E
authors.initials: HE
authors.lastname: Speedy
authors.affiliation: 1] Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK. [2].
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Di Bernardo
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Georgina P
authors.initials: GP
authors.lastname: Sava
authors.affiliation: Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: Holroyd
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Sunter
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Larry
authors.initials: L
authors.lastname: Mansouri
authors.affiliation: Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Hematology and Transplantation, Lund University, Lund, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Juliusson
authors.affiliation: Unit of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karin E
authors.initials: KE
authors.lastname: Smedby
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Roos
authors.affiliation: Medical Research Council Toxicology Unit, Leicester University, Leicester, UK.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Jayne
authors.affiliation: Medical Research Council Toxicology Unit, Leicester University, Leicester, UK.
authors.forename: Aneela
authors.initials: A
authors.lastname: Majid
authors.affiliation: Haemato-Oncology, Division of Molecular Pathology, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Dearden
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Hall
authors.affiliation: Haematological Sciences, Medical School, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: Tryfonia
authors.initials: T
authors.lastname: Mainou-Fowler
authors.affiliation: Department of Haematology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK.
authors.forename: Graham H
authors.initials: GH
authors.lastname: Jackson
authors.affiliation: Department of Haematology, Queen Elizabeth Hospital, Gateshead, Newcastle-upon-Tyne, UK.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Summerfield
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Harris
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Pettitt
authors.affiliation: Department of Haematology, Hull Royal Infirmary, Hull, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Allsup
authors.affiliation: Hull York Medical School and University of Hull, Hull, UK.
authors.forename: James R
authors.initials: JR
authors.lastname: Bailey
authors.affiliation: Department of Haematology, Birmingham Heartlands Hospital, Birmingham, UK.
authors.forename: Guy
authors.initials: G
authors.lastname: Pratt
authors.affiliation: Department of Haematology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Pepper
authors.affiliation: Cardiff and Vale National Health Service Trust, Heath Park, Cardiff, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Fegan
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
authors.affiliation: Haemato-Oncology, Division of Molecular Pathology, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: James M
authors.initials: JM
authors.lastname: Allan
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002893:Chromosomes, Human, Pair 3; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins / Q000235:genetics
chemical_list: C422445:CLPTM1L protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C440849:POT1 protein, human; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins