A genome-wide association analysis reveals new pathogenic pathways in gout

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023728%3A_____%2F24%3AN0000007" target="_blank" >RIV/00023728:_____/24:N0000007 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00023728:_____/24:N0000045 RIV/00216208:11110/24:10492940 RIV/00064165:_____/24:10492940

Výsledek na webu

<a href="https://doi.org/10.1038/s41588-024-01921-5" target="_blank" >https://doi.org/10.1038/s41588-024-01921-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41588-024-01921-5" target="_blank" >10.1038/s41588-024-01921-5</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A genome-wide association analysis reveals new pathogenic pathways in gout

Popis výsledku v původním jazyce

Gout is a chronic disease that is caused by an innate immune response to deposited monosodium urate crystals in the setting of hyperuricemia. Here, we provide insights into the molecular mechanism of the poorly understood inflammatory component of gout from a genome-wide association study (GWAS) of 2.6 million people, including 120,295 people with prevalent gout. We detected 377 loci and 410 genetically independent signals (149 previously unreported loci in urate and gout). An additional 65 loci with signals in urate (from a GWAS of 630,117 individuals) but not gout were identified. A prioritization scheme identified candidate genes in the inflammatory process of gout, including genes involved in epigenetic remodeling, cell osmolarity and regulation of NOD-like receptor protein 3 (NLRP3) inflammasome activity. Mendelian randomization analysis provided evidence for a causal role of clonal hematopoiesis of indeterminate potential in gout. Our study identifies candidate genes and molecular processes in the inflammatory pathogenesis of gout suitable for follow-up studies.

Název v anglickém jazyce

A genome-wide association analysis reveals new pathogenic pathways in gout

Popis výsledku anglicky

Gout is a chronic disease that is caused by an innate immune response to deposited monosodium urate crystals in the setting of hyperuricemia. Here, we provide insights into the molecular mechanism of the poorly understood inflammatory component of gout from a genome-wide association study (GWAS) of 2.6 million people, including 120,295 people with prevalent gout. We detected 377 loci and 410 genetically independent signals (149 previously unreported loci in urate and gout). An additional 65 loci with signals in urate (from a GWAS of 630,117 individuals) but not gout were identified. A prioritization scheme identified candidate genes in the inflammatory process of gout, including genes involved in epigenetic remodeling, cell osmolarity and regulation of NOD-like receptor protein 3 (NLRP3) inflammasome activity. Mendelian randomization analysis provided evidence for a causal role of clonal hematopoiesis of indeterminate potential in gout. Our study identifies candidate genes and molecular processes in the inflammatory pathogenesis of gout suitable for follow-up studies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Nature Genetic

ISSN

1061-4036

e-ISSN

1546-1718

Svazek periodika

56

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

2392-2406

Kód UT WoS článku

001409740700001

EID výsledku v databázi Scopus

2-s2.0-85206813683