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

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Serval ID
serval:BIB_91EB9553973D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
UNIL/CHUV
Title
A genome-wide association analysis reveals new pathogenic pathways in gout.
Journal
Nature genetics
Author(s)
Major T.J., Takei R., Matsuo H., Leask M.P., Sumpter N.A., Topless R.K., Shirai Y., Wang W., Cadzow M.J., Phipps-Green A.J., Li Z., Ji A., Merriman M.E., Morice E., Kelley E.E., Wei W.H., McCormick SPA, Bixley M.J., Reynolds R.J., Saag K.G., Fadason T., Golovina E., O'Sullivan J.M., Stamp L.K., Dalbeth N., Abhishek A., Doherty M., Roddy E., Jacobsson LTH, Kapetanovic M.C., Melander O., Andrés M., Pérez-Ruiz F., Torres R.J., Radstake T., Jansen T.L., Janssen M., Joosten LAB, Liu R., Gaal O.I., Crişan T.O., Rednic S., Kurreeman F., Huizinga TWJ, Toes R., Lioté F., Richette P., Bardin T., Ea H.K., Pascart T., McCarthy G.M., Helbert L., Stibůrková B., Tausche A.K., Uhlig T., Vitart V., Boutin T.S., Hayward C., Riches P.L., Ralston S.H., Campbell A., MacDonald T.M., Nakayama A., Takada T., Nakatochi M., Shimizu S., Kawamura Y., Toyoda Y., Nakaoka H., Yamamoto K., Matsuo K., Shinomiya N., Ichida K., Lee C., Bradbury L.A., Brown M.A., Robinson P.C., Buchanan RRC, Hill C.L., Lester S., Smith M.D., Rischmueller M., Choi H.K., Stahl E.A., Miner J.N., Solomon D.H., Cui J., Giacomini K.M., Brackman D.J., Jorgenson E.M., Liu H., Susztak K., Shringarpure S., So A., Okada Y., Li C., Shi Y., Merriman T.R.
Working group(s)
FAST Study Group, Japan Gout Genomics Consortium, Asia Pacific Gout Consortium, GlobalGout Genetics Consortium, 23andMe Research Team
Contributor(s)
Shringapure S.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
11/2024
Peer-reviewed
Oui
Editor
Shringapure S., Fast Study Group Japan Gout Genomics Consortium Asia Pacific Gout Consortium GlobalGout Genetics Consortium andMe Research Team
Volume
56
Number
11
Pages
2392-2406
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
Gout/genetics, Genome-Wide Association Study, Humans, Genetic Predisposition to Disease, Uric Acid, Polymorphism, Single Nucleotide, Mendelian Randomization Analysis, NLR Family, Pyrin Domain-Containing 3 Protein/genetics, Male, Hyperuricemia/genetics
OAI-PMH
oai:serval.unil.ch:BIB_91EB9553973D
DOI
10.1038/s41588-024-01921-5
Pubmed
39406924
Create date
25/10/2024 13:38
Last modification date
19/11/2024 7:23
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