Karina Dalsgaard Sørensen

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Molly Went, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
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  • Amit Sud, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
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  • Asta Försti, Center for Primary Health Care Research, Lund University, SE-205 02, Malmo, Sweden.
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  • Britt-Marie Halvarsson, Hematology and Transfusion Medicine, Department of Laboratory Medicine, BMC B13, Lund University, SE-221 84, Lund, Sweden.
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  • Niels Weinhold, Department of Internal Medicine V, University of Heidelberg, 69117, Heidelberg, Germany.
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  • Scott Kimber, Division of Molecular Pathology, The Institute of Cancer Research, London, SW7 3RP, UK.
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  • Mark van Duin, Department of Hematology, Erasmus MC Cancer Institute, 3075 EA, Rotterdam, The Netherlands.
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  • Gudmar Thorleifsson, deCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
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  • Amy Holroyd, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
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  • David C Johnson, Division of Molecular Pathology, The Institute of Cancer Research, London, SW7 3RP, UK.
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  • Ni Li, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
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  • Giulia Orlando, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
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  • Philip J Law, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
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  • Mina Ali, Hematology and Transfusion Medicine, Department of Laboratory Medicine, BMC B13, Lund University, SE-221 84, Lund, Sweden.
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  • Bowang Chen, Division of Cancer Epidemiology, German Cancer Research Center, 69120 Heidelberg, Germany.
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  • Jonathan S Mitchell, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
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  • Daniel F Gudbjartsson, School of Engineering and Natural Sciences, University of Iceland, IS-101, Reykjavik, Iceland.
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  • Rowan Kuiper, Department of Hematology, Erasmus MC Cancer Institute, 3075 EA, Rotterdam, The Netherlands.
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  • Owen W Stephens, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
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  • Uta Bertsch, National Centre of Tumor Diseases, 69120, Heidelberg, Germany.
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  • Peter Broderick, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
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  • Chiara Campo, Division of Cancer Epidemiology, German Cancer Research Center, 69120 Heidelberg, Germany.
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  • Obul R Bandapalli, Division of Cancer Epidemiology, German Cancer Research Center, 69120 Heidelberg, Germany.
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  • Hermann Einsele, University Clinic of Würzburg, 97080, Würzburg, Germany.
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  • Walter A Gregory, Clinical Trials Research Unit, University of Leeds, Leeds, LS2 9PH, UK.
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  • Urban Gullberg, Hematology and Transfusion Medicine, Department of Laboratory Medicine, BMC B13, Lund University, SE-221 84, Lund, Sweden.
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  • Jens Hillengass, Department of Internal Medicine V, University of Heidelberg, 69117, Heidelberg, Germany.
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  • Per Hoffmann, Division of Medical Genetics, Department of Biomedicine, University of Basel, 4003, Basel, Switzerland.
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  • Graham H Jackson, Institute of Health and Society, Newcastle University, Sir James Spence Institute, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK. Electronic address: lindsay.pennington@ncl.ac.uk.
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  • Karl-Heinz Jöckel, Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany.
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  • Ellinor Johnsson, Hematology and Transfusion Medicine, Department of Laboratory Medicine, BMC B13, Lund University, SE-221 84, Lund, Sweden.
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  • Sigurður Y Kristinsson, Department of Hematology, Landspitali, National University Hospital of Iceland, IS-101, Reykjavik, Iceland.
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  • Ulf-Henrik Mellqvist, Section of Hematology, Sahlgrenska University Hospital, Gothenburg, 413 45, Sweden.
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  • Hareth Nahi, Center for Hematology and Regenerative Medicine, SE-171 77, Stockholm, Sweden.
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  • Douglas Easton, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
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  • Paul Pharoah, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
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  • Alison Dunning, Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge CB1 8RN, UK.
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  • Julian Peto, Non-communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
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  • Federico Canzian, Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
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  • Anthony Swerdlow, Division of Breast Cancer Research, The Institute of Cancer Research, London, SW7 3RP, UK.
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  • Rosalind A Eeles, Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.
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  • ZSofia Kote-Jarai, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
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  • Kenneth Muir, Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom.
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  • Nora Pashayan, Department of Applied Health Research, University College London, London, WC1E 7HB, UK.
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  • Jolanta Nickel, Department of Internal Medicine V, University of Heidelberg, 69117, Heidelberg, Germany.
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  • Markus M Nöthen, 1] Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, D-53127 Bonn, Germany.
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  • Thorunn Rafnar, deCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
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  • Hauke Thomsen, Division of Cancer Epidemiology, German Cancer Research Center, 69120 Heidelberg, Germany.
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  • The PRACTICAL Consortium
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  • Niels Frost Andersen (Member of author collaboration)
  • Karina Dalsgaard Sørensen (Member of author collaboration)

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.

Original languageEnglish
Article number3707
JournalNature Communications
Volume9
Issue1
Pages (from-to)3707
Number of pages10
ISSN2041-1723
DOIs
Publication statusPublished - 13 Sep 2018

    Research areas

  • Bayes Theorem, Chromatin/chemistry, Chromatin Immunoprecipitation, European Continental Ancestry Group/genetics, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Multiple Myeloma/genetics, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Quality Control, Quantitative Trait Loci, Risk, CASE-CONTROL ASSOCIATION, SOCS BOX, GENE-EXPRESSION, CELLS, COMPLEX, ANKYRIN REPEAT, POLYMORPHISM, HERITABILITY, TACI, ARCHITECTURE

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