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

Details

Serval ID
serval:BIB_91EB9553973D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
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
In Press
Peer-reviewed
Oui
Editor
Shringapure S., Fast Study Group Japan Gout Genomics Consortium Asia Pacific Gout Consortium GlobalGout Genetics Consortium andMe Research Team
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
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.
Pubmed
Create date
25/10/2024 13:38
Last modification date
26/10/2024 6:12
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