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Enrichment of B cel...
Enrichment of B cell receptor signaling and epidermal growth factor receptor pathways in monoclonal gammopathy of undetermined significance : a genome-wide genetic interaction study
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- Chattopadhyay, Subhayan (författare)
- Heidelberg University,German Cancer Research Centre
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- Thomsen, Hauke (författare)
- German Cancer Research Centre
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- da Silva Filho, Miguel Inacio (författare)
- German Cancer Research Centre
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- Weinhold, Niels (författare)
- University of Arkansas for Medical Sciences
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- Hoffmann, Per (författare)
- University of Basel
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- Nöthen, Markus M (författare)
- University of Bonn
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- Marina, Arendt (författare)
- University of Duisburg-Essen
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- Jöckel, Karl-Heinz (författare)
- University of Duisburg-Essen
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- Schmidt, Börge (författare)
- University of Duisburg-Essen
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- Pechlivanis, Sonali (författare)
- University of Duisburg-Essen
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- Langer, Christian (författare)
- University of Ulm
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- Goldschmidt, Hartmut (författare)
- National Centre of Tumor Diseases
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- Hemminki, Kari (författare)
- 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 (författare)
- 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)
- 2018-06-11
- 2018
- Engelska.
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Ingår i: Molecular Medicine. - : Springer Science and Business Media LLC. - 1528-3658 .- 1076-1551. ; 24:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://molmed.biome...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- BACKGROUND: Recent identification of 10 germline variants predisposing to monoclonal gammopathy of undetermined significance (MGUS) explicates genetic dependency of this asymptomatic precursor condition with multiple myeloma (MM). Yet much of genetic burden as well as functional links remain unexplained. We propose a workflow to expand the search for susceptibility loci with genome-wide interaction and for subsequent identification of genetic clusters and pathways.METHODS: Polygenic interaction analysis on 243 cases/1285 controls identified 14 paired risk loci belonging to unique chromosomal bands which were then replicated in two independent sets (case only study, 82 individuals; case/control study 236 cases/ 2484 controls). Further investigation on gene-set enrichment, regulatory pathway and genetic network was carried out with stand-alone in silico tools separately for both interaction and genome-wide association study-detected risk loci.RESULTS: Intronic-PREX1 (20q13.13), a reported locus predisposing to MM was confirmed to have contribution to excess MGUS risk in interaction with SETBP1, a well-established candidate predisposing to myeloid malignancies. Pathway enrichment showed B cell receptor signaling pathway (P < 5.3 × 10- 3) downstream to allograft rejection pathway (P < 5.6 × 10- 4) and autoimmune thyroid disease pathway (P < 9.3 × 10- 4) as well as epidermal growth factor receptor regulation pathway (P < 2.4 × 10- 2) to be differentially regulated. Oncogene ALK and CDH2 were also identified to be moderately interacting with rs10251201 and rs16966921, two previously reported risk loci for MGUS.CONCLUSIONS: We described novel pathways and variants potentially causal for MGUS. The methodology thus proposed to facilitate our search streamlines risk locus-based interaction, genetic network and pathway enrichment analyses.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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Chattopadhyay, S ...
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Thomsen, Hauke
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da Silva Filho, ...
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Weinhold, Niels
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Hoffmann, Per
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Nöthen, Markus M
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visa fler...
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Marina, Arendt
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Jöckel, Karl-Hei ...
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Schmidt, Börge
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Pechlivanis, Son ...
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Langer, Christia ...
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Goldschmidt, Har ...
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Hemminki, Kari
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Försti, Asta
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