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Deciphering the gen...
Deciphering the genetics and mechanisms of predisposition to multiple myeloma
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- Went, Molly (author)
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom
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- Duran-Lozano, Laura (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Center,Division of stem cell research,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
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- Halldorsson, Gisli H. (author)
- deCODE Genetics/Amgen, Reykjavik, Iceland
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show more...
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- Gunnell, Andrea (author)
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom
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- Ugidos-Damboriena, Nerea (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Hematogenomics,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Center,Division of stem cell research,Lund University Research Groups,Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
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- Law, Philip (author)
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom
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- Ekdahl, Ludvig (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
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- Sud, Amit (author)
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom
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- Thorleifsson, Gudmar (author)
- deCODE Genetics/Amgen, Sturlugata 8, Reykjavik, Iceland
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- Thodberg, Malte (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematogenomics,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
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- Olafsdottir, Thorunn (author)
- deCODE Genetics/Amgen, Reykjavik, Iceland
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- Lamarca-Arrizabalaga, Antton (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
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- Cafaro, Caterina (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
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- Niroula, Abhishek (author)
- Lund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
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- Ajore, Ram (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
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- Lopez de Lapuente Portilla, Aitzkoa (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
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- Ali, Zain (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
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- Pertesi, Maroulio (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
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- Goldschmidt, Hartmut (author)
- Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
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- Stefansdottir, Lilja (author)
- deCODE Genetics/Amgen, Reykjavik, Iceland
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- Kristinsson, Sigurdur Y. (author)
- Landspitali, National University Hospital of Iceland, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland,National University Hospital of Iceland
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- Stacey, Simon N. (author)
- deCODE Genetics/Amgen, Reykjavik, Iceland
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- Love, Thorvardur J. (author)
- Landspitali, National University Hospital of Iceland, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland,University of Iceland
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- Rognvaldsson, Saemundur (author)
- Landspitali, National University Hospital of Iceland, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland,University of Iceland
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- Hajek, Roman (author)
- University Hospital Ostrava and University of Ostrava, Ostrava, Czech Republic
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- Vodicka, Pavel (author)
- Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic
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- Pettersson-Kymmer, Ulrika (author)
- Umeå universitet,Umeå University,Institutionen för integrativ medicinsk biologi (IMB)
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- Späth, Florentin, 1980- (author)
- Umeå universitet,Umeå University,Institutionen för strålningsvetenskaper
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- Schinke, Carolina (author)
- Myeloma Center, University of Arkansas for Medical Sciences, AR, Little Rock, United States
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- Van Rhee, Frits (author)
- Myeloma Center, University of Arkansas for Medical Sciences, AR, Little Rock, United States
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- Sulem, Patrick (author)
- deCODE Genetics/Amgen, Reykjavik, Iceland
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- Ferkingstad, Egil (author)
- deCODE Genetics/Amgen, Reykjavik, Iceland
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- Hjorleifsson Eldjarn, Grimur (author)
- deCODE Genetics/Amgen, Reykjavik, Iceland
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- Mellqvist, Ulf Henrik (author)
- South Elfsborg Hospital,Southern Älvsborg Hospital, Borås, Sweden
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- Jonsdottir, Ingileif (author)
- deCODE Genetics/Amgen, Reykjavik, Iceland
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- Morgan, Gareth (author)
- Perlmutter Cancer Center, Langone Health, New York University, NY, New York, United States
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- Sonneveld, Pieter (author)
- Erasmus University Medical Center,Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands
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- Waage, Anders (author)
- Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
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- Weinhold, Niels (author)
- Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany,German Cancer Research Centre
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- Thomsen, Hauke (author)
- MSB Medical School Berlin, Berlin, Germany
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- Försti, Asta (author)
- Hopp Children’s Cancer Center Heidelberg (KiTZ),German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children’s Cancer Center, Heidelberg, Germany
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- Hansson, Markus (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Myelomgruppen,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Myeloma research group,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Department of Laboratory Medicine, Lund University, Lund, Sweden; Section of Hematology, Sahlgrenska University Hospital, Gothenburg, Sweden; Skåne University Hospital, Lund, Sweden,Sahlgrenska University Hospital
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- Juul-Vangsted, Annette (author)
- Department of Haematology, University Hospital of Copenhagen at Rigshospitalet, Copenhagen, Denmark
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- Thorsteinsdottir, Unnur (author)
- deCODE Genetics/Amgen, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland,University of Iceland
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- Hemminki, Kari (author)
- Charles University in Prague,German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
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- Kaiser, Martin (author)
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom
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- Rafnar, Thorunn (author)
- deCODE Genetics/Amgen, Reykjavik, Iceland
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- Stefansson, Kari (author)
- deCODE Genetics/Amgen, , Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland,University of Iceland
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- Houlston, Richard (author)
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom
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- Nilsson, Björn (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Center,Division of stem cell research,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden; Broad Institute, MA, Cambridge, United States
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(creator_code:org_t)
- Springer Nature, 2024
- 2024
- English.
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
- Related links:
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http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- Multiple myeloma (MM) is an incurable malignancy of plasma cells. Epidemiological studies indicate a substantial heritable component, but the underlying mechanisms remain unclear. Here, in a genome-wide association study totaling 10,906 cases and 366,221 controls, we identify 35 MM risk loci, 12 of which are novel. Through functional fine-mapping and Mendelian randomization, we uncover two causal mechanisms for inherited MM risk: longer telomeres; and elevated levels of B-cell maturation antigen (BCMA) and interleukin-5 receptor alpha (IL5RA) in plasma. The largest increase in BCMA and IL5RA levels is mediated by the risk variant rs34562254-A at TNFRSF13B. While individuals with loss-of-function variants in TNFRSF13B develop B-cell immunodeficiency, rs34562254-A exerts a gain-of-function effect, increasing MM risk through amplified B-cell responses. Our results represent an analysis of genetic MM predisposition, highlighting causal mechanisms contributing to MM development.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Went, Molly
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Duran-Lozano, La ...
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Halldorsson, Gis ...
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Gunnell, Andrea
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Ugidos-Damborien ...
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Law, Philip
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show more...
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Ekdahl, Ludvig
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Sud, Amit
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Thorleifsson, Gu ...
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Thodberg, Malte
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Olafsdottir, Tho ...
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Lamarca-Arrizaba ...
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Cafaro, Caterina
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Niroula, Abhishe ...
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Ajore, Ram
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Lopez de Lapuent ...
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Ali, Zain
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Pertesi, Marouli ...
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Goldschmidt, Har ...
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Stefansdottir, L ...
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Kristinsson, Sig ...
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Stacey, Simon N.
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Love, Thorvardur ...
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Rognvaldsson, Sa ...
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Hajek, Roman
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Vodicka, Pavel
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Pettersson-Kymme ...
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Späth, Florentin ...
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Schinke, Carolin ...
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Van Rhee, Frits
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Sulem, Patrick
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Ferkingstad, Egi ...
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Hjorleifsson Eld ...
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Mellqvist, Ulf H ...
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Jonsdottir, Ingi ...
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Morgan, Gareth
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Sonneveld, Piete ...
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Waage, Anders
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Weinhold, Niels
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Thomsen, Hauke
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Försti, Asta
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Hansson, Markus
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Juul-Vangsted, A ...
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Thorsteinsdottir ...
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Hemminki, Kari
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Kaiser, Martin
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Rafnar, Thorunn
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Stefansson, Kari
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Houlston, Richar ...
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Nilsson, Björn
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Nature Communica ...
- By the university
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Lund University
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Umeå University