Genomewide association study on monoclonal gammopathy of unknown significance (MGUS)
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
28375557
DOI
10.1111/ejh.12892
Knihovny.cz E-zdroje
- Klíčová slova
- germ line, low-risk genes, myeloma, susceptibility,
- MeSH
- alely MeSH
- celogenomová asociační studie * MeSH
- genetická predispozice k nemoci * MeSH
- genotyp MeSH
- hodnocení rizik MeSH
- jednonukleotidový polymorfismus MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokus kvantitativního znaku MeSH
- monoklonální gamapatie nejasného významu diagnóza genetika MeSH
- odds ratio MeSH
- senioři MeSH
- srovnávací genomová hybridizace MeSH
- vazebná nerovnováha MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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.
Center for Primary Health Care Research Lund University Malmö Sweden
Department of Biomedicine University of Basel Basel Switzerland
Department of Genomics Life and Brain Research Center University of Bonn Bonn Germany
Department of Hematology University Hospital Kralovske Vinohrady Prague Czech Republic
Department of Hematooncology University Hospital Ostrava Ostrava Czech Republic
Department of Internal Medicine 3 University of Ulm Ulm Germany
Department of Internal Medicine 5 University of Heidelberg Heidelberg Germany
Department of Internal Medicine Hematology and Oncology University Hospital Brno Brno Czech Republic
Division of Molecular Genetic Epidemiology German Cancer Research Center Heidelberg Germany
Faculty of Medicine and Biomedical Center in Pilsen Charles University Prague Pilsen Czech Republic
Institute of Experimental Medicine Academy of Sciences of the Czech Republic Prague Czech Republic
Institute of Human Genetics University of Bonn Bonn Germany
Myeloma Institute University of Arkansas for Medical Sciences Little Rock AR USA
Citace poskytuje Crossref.org
Epidemiology, genetics and treatment of multiple myeloma and precursor diseases
