Genome-wide meta-analysis of monoclonal gammopathy of undetermined significance (MGUS) identifies risk loci impacting IRF-6

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00843989%3A_____%2F22%3AE0109550" target="_blank" >RIV/00843989:_____/22:E0109550 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/22:10443287 RIV/00216208:11140/22:10443287 RIV/61988987:17110/22:A2302FMO RIV/68378041:_____/22:00567831

Výsledek na webu

<a href="https://www.nature.com/articles/s41408-022-00658-w.pdf" target="_blank" >https://www.nature.com/articles/s41408-022-00658-w.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41408-022-00658-w" target="_blank" >10.1038/s41408-022-00658-w</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Genome-wide meta-analysis of monoclonal gammopathy of undetermined significance (MGUS) identifies risk loci impacting IRF-6

Popis výsledku v původním jazyce

Monoclonal gammopathy of undetermined significance (MGUS) is a benign plasma cell disorder, common in the Western population (3–5% ?50 years) and characterized by an asymptomatic clonal plasma cell expansion [1]. MGUS progresses to multiple myeloma (MM) at a rate of 1% per year [1], but can also progress to light chain amyloidosis (AL amyloidosis), Waldenström macroglobulinemia, and lymphoma. Familial clustering of MGUS or MM support the role for genetic susceptibility [2]. MM and MGUS have shared heritability, with a genetic correlation of 55% and SNP-based heritability estimates of 17% and 15%, respectively (3,4). This suggests a large portion of missing heritability to be identified. Previous genome-wide association studies (GWAS) have successfully identified 24 common loci associated with MM risk [3, 4]; of these, 12 are also associated with MGUS [5]. Twenty additional loci have been identified for risk of MGUS but the impact of these loci on progression is unknown [5, 6]. Identifying additional common variants contributing to MGUS may elucidate the unaccounted missing heritability for both MGUS and MM. Further, understanding genetic determinants of MGUS are important regardless of MM, given the associations of MGUS with multiple conditions, not just MM. In this study, we performed the largest MGUS GWAS meta-analysis to date and validated associations of known MM/MGUS risk variants.

Název v anglickém jazyce

Genome-wide meta-analysis of monoclonal gammopathy of undetermined significance (MGUS) identifies risk loci impacting IRF-6

Popis výsledku anglicky

Monoclonal gammopathy of undetermined significance (MGUS) is a benign plasma cell disorder, common in the Western population (3–5% ?50 years) and characterized by an asymptomatic clonal plasma cell expansion [1]. MGUS progresses to multiple myeloma (MM) at a rate of 1% per year [1], but can also progress to light chain amyloidosis (AL amyloidosis), Waldenström macroglobulinemia, and lymphoma. Familial clustering of MGUS or MM support the role for genetic susceptibility [2]. MM and MGUS have shared heritability, with a genetic correlation of 55% and SNP-based heritability estimates of 17% and 15%, respectively (3,4). This suggests a large portion of missing heritability to be identified. Previous genome-wide association studies (GWAS) have successfully identified 24 common loci associated with MM risk [3, 4]; of these, 12 are also associated with MGUS [5]. Twenty additional loci have been identified for risk of MGUS but the impact of these loci on progression is unknown [5, 6]. Identifying additional common variants contributing to MGUS may elucidate the unaccounted missing heritability for both MGUS and MM. Further, understanding genetic determinants of MGUS are important regardless of MM, given the associations of MGUS with multiple conditions, not just MM. In this study, we performed the largest MGUS GWAS meta-analysis to date and validated associations of known MM/MGUS risk variants.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Blood cancer journal

ISSN

2044-5385

e-ISSN

2044-5385

Svazek periodika

16

Číslo periodika v rámci svazku

article 60

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

5

Strana od-do

1-5

Kód UT WoS článku

000783707700002

EID výsledku v databázi Scopus

2-s2.0-85128121039