Genomewide association study on monoclonal gammopathy of unknown significance (MGUS)

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F17%3A00476864" target="_blank" >RIV/68378041:_____/17:00476864 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/17:10364000 RIV/00216208:11140/17:10364000 RIV/65269705:_____/17:00067552 RIV/00064173:_____/17:N0000033 RIV/00843989:_____/17:E0106412

Výsledek na webu

<a href="http://dx.doi.org/10.1111/ejh.12892" target="_blank" >http://dx.doi.org/10.1111/ejh.12892</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/ejh.12892" target="_blank" >10.1111/ejh.12892</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Genomewide association study on monoclonal gammopathy of unknown significance (MGUS)

Popis výsledku v původním jazyce

ObjectivesTo identify germ line variants contributing to the development of monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic premalignant precursor for multiple myeloma (MM). nnMethodsWe 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. nnResultsIn 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=2.94x10(-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. nnConclusionsThese 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.

Název v anglickém jazyce

Genomewide association study on monoclonal gammopathy of unknown significance (MGUS)

Popis výsledku anglicky

ObjectivesTo identify germ line variants contributing to the development of monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic premalignant precursor for multiple myeloma (MM). nnMethodsWe 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. nnResultsIn 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=2.94x10(-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. nnConclusionsThese 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LO1503" target="_blank" >LO1503: BIOMEDIC</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Haematology

ISSN

0902-4441

e-ISSN

—

Svazek periodika

99

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

DK - Dánské království

Počet stran výsledku

10

Strana od-do

70-79

Kód UT WoS článku

000403724300009

EID výsledku v databázi Scopus

2-s2.0-85019753807