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Genomewide associat...
Genomewide association study on monoclonal gammopathy of unknown significance (MGUS)
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- Thomsen, Hauke (author)
- German Cancer Research Centre
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- Campo, Chiara (author)
- German Cancer Research Centre
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- Weinhold, Niels (author)
- University of Arkansas for Medical Sciences
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- da Silva Filho, Miguel Inacio (author)
- German Cancer Research Centre
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- Pour, Luděk (author)
- University Hospital Brno
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- Gregora, Evžen (author)
- University Hospital Kralovske Vinohrady
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- Vodicka, Pavel (author)
- Charles University in Prague
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- Vodickova, Ludmila (author)
- Charles University in Prague
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- Hoffmann, Per (author)
- University of Basel
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- Nöthen, Markus M (author)
- University of Bonn
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- Jöckel, Karl-Heinz (author)
- University of Duisburg-Essen
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- Langer, Christian (author)
- University of Ulm
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- Hajek, Roman (author)
- University Hospital Ostrava
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- Goldschmidt, Hartmut (author)
- Heidelberg University
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- Hemminki, Kari (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups,German Cancer Research Centre
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- Försti, Asta (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups,German Cancer Research Centre
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(creator_code:org_t)
- 2017-05-24
- 2017
- English 10 s.
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In: European Journal of Haematology. - : Wiley. - 0902-4441. ; 99:1, s. 70-79
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http://dx.doi.org/10...
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Abstract
Subject headings
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- OBJECTIVES: To identify germ line variants contributing to the development of monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic premalignant precursor for multiple myeloma (MM).METHODS: We conducted the first genomewide association study (GWAS) on MGUS on 243 German cases with a replication on 294 Czech cases. Identified loci were further analyzed in 1508 German MM patients. New MM loci recently reported in a meta-analysis were also tested in the MGUS GWAS.RESULTS: In GWAS, we identified 10 loci contributing to development of MGUS at P-value threshold of 10-5 . The Czech cohort gave support for two associations (6q26, rs6933936; 7p21.3 rs10251201). In GWAS, rs974120 (8p23.2) reached genomewide significance (P=2.94×10-9 ), with a nominal significance in MM. The locus of rs974120 shows marks of transcriptional activity in leukemia according to ENCODE data. rs10251201 (7p21.3), rs9318227 (13q22.1), and rs10405859 (19q13.32) were associated with markers related to leukemogenesis and immune and inflammatory responses. Two newly identified candidate loci for MM, rs1948915 (8q24.21) and rs8058578 (16p11.2), were nominally associated with MGUS.CONCLUSIONS: These data allow a cautious first proposal for a germ line architecture of MGUS with links to leukemia and autoimmune conditions, the latter agreeing with a family study showing clustering of MGUS with autoimmune diseases.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- Germ line
- Low-risk genes
- Myeloma
- Susceptibility
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Thomsen, Hauke
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Campo, Chiara
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Weinhold, Niels
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da Silva Filho, ...
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Pour, Luděk
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Gregora, Evžen
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show more...
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Vodicka, Pavel
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Vodickova, Ludmi ...
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Hoffmann, Per
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Nöthen, Markus M
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Jöckel, Karl-Hei ...
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Langer, Christia ...
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Hajek, Roman
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Goldschmidt, Har ...
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Hemminki, Kari
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Försti, Asta
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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 Basic Medicine
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and Medical Genetics
- Articles in the publication
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European Journal ...
- By the university
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Lund University