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Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma.
Went, Molly; Sud, Amit; Försti, Asta; Halvarsson, Britt-Marie; Weinhold, Niels; Kimber, Scott; van Duin, Mark; Thorleifsson, Gudmar; Holroyd, Amy; Johnson, David C; Li, Ni; Orlando, Giulia; Law, Philip J; Ali, Mina; Chen, Bowang; Mitchell, Jonathan S; Gudbjartsson, Daniel F; Kuiper, Rowan; Stephens, Owen W; Bertsch, Uta; Broderick, Peter; Campo, Chiara; Bandapalli, Obul R; Einsele, Hermann; Gregory, Walter A; Gullberg, Urban; Hillengass, Jens; Hoffmann, Per; Jackson, Graham H; Jöckel, Karl-Heinz; Johnsson, Ellinor; Kristinsson, Sigurður Y; Mellqvist, Ulf-Henrik; Nahi, Hareth; Easton, Douglas; Pharoah, Paul; Dunning, Alison; Peto, Julian; Canzian, Federico; Swerdlow, Anthony; Eeles, Rosalind A; Kote-Jarai, ZSofia; Muir, Kenneth; Pashayan, Nora; Nickel, Jolanta; Nöthen, Markus M; Rafnar, Thorunn; Ross, Fiona M; da Silva Filho, Miguel Inacio; Thomsen, Hauke.
Afiliação
  • Went M; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • Sud A; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • Försti A; German Cancer Research Center, 69120, Heidelberg, Germany.
  • Halvarsson BM; Center for Primary Health Care Research, Lund University, SE-205 02, Malmo, Sweden.
  • Weinhold N; Hematology and Transfusion Medicine, Department of Laboratory Medicine, BMC B13, Lund University, SE-221 84, Lund, Sweden.
  • Kimber S; Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
  • van Duin M; Department of Internal Medicine V, University of Heidelberg, 69117, Heidelberg, Germany.
  • Thorleifsson G; Division of Molecular Pathology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • Holroyd A; Department of Hematology, Erasmus MC Cancer Institute, 3075 EA, Rotterdam, The Netherlands.
  • Johnson DC; deCODE Genetics, Sturlugata 8, IS-101, Reykjavik, Iceland.
  • Li N; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • Orlando G; Division of Molecular Pathology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • Law PJ; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • Ali M; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • Chen B; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • Mitchell JS; Hematology and Transfusion Medicine, Department of Laboratory Medicine, BMC B13, Lund University, SE-221 84, Lund, Sweden.
  • Gudbjartsson DF; German Cancer Research Center, 69120, Heidelberg, Germany.
  • Kuiper R; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • Stephens OW; deCODE Genetics, Sturlugata 8, IS-101, Reykjavik, Iceland.
  • Bertsch U; School of Engineering and Natural Sciences, University of Iceland, IS-101, Reykjavik, Iceland.
  • Broderick P; Department of Hematology, Erasmus MC Cancer Institute, 3075 EA, Rotterdam, The Netherlands.
  • Campo C; Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
  • Bandapalli OR; German Cancer Research Center, 69120, Heidelberg, Germany.
  • Einsele H; National Centre of Tumor Diseases, 69120, Heidelberg, Germany.
  • Gregory WA; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • Gullberg U; German Cancer Research Center, 69120, Heidelberg, Germany.
  • Hillengass J; German Cancer Research Center, 69120, Heidelberg, Germany.
  • Hoffmann P; University Clinic of Würzburg, 97080, Würzburg, Germany.
  • Jackson GH; Clinical Trials Research Unit, University of Leeds, Leeds, LS2 9PH, UK.
  • Jöckel KH; Hematology and Transfusion Medicine, Department of Laboratory Medicine, BMC B13, Lund University, SE-221 84, Lund, Sweden.
  • Johnsson E; Department of Internal Medicine V, University of Heidelberg, 69117, Heidelberg, Germany.
  • Kristinsson SY; Institute of Human Genetics, University of Bonn, D-53127, Bonn, Germany.
  • Mellqvist UH; Division of Medical Genetics, Department of Biomedicine, University of Basel, 4003, Basel, Switzerland.
  • Nahi H; Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK.
  • Easton D; Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, D-45147, Germany.
  • Pharoah P; Hematology and Transfusion Medicine, Department of Laboratory Medicine, BMC B13, Lund University, SE-221 84, Lund, Sweden.
  • Dunning A; Department of Hematology, Landspitali, National University Hospital of Iceland, IS-101, Reykjavik, Iceland.
  • Peto J; Section of Hematology, Sahlgrenska University Hospital, Gothenburg, 413 45, Sweden.
  • Canzian F; Center for Hematology and Regenerative Medicine, SE-171 77, Stockholm, Sweden.
  • Swerdlow A; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.
  • Eeles RA; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
  • Kote-Jarai Z; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.
  • Muir K; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
  • Pashayan N; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.
  • Nickel J; Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
  • Nöthen MM; Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany.
  • Rafnar T; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • Ross FM; Division of Breast Cancer Research, The Institute of Cancer Research, London, SW7 3RP, UK.
  • da Silva Filho MI; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • Thomsen H; Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.
Nat Commun ; 9(1): 3707, 2018 09 13.
Article em En | MEDLINE | ID: mdl-30213928
ABSTRACT
Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Mieloma Múltiplo Tipo de estudo: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Female / Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Mieloma Múltiplo Tipo de estudo: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Female / Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Reino Unido