| Title: | A genome-wide association analysis reveals new pathogenic pathways in gout |
| Journal: | Nature Genetics |
| Published: | 15 Oct 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39406924/ |
| DOI: | https://doi.org/10.1038/s41588-024-01921-5 |
Publication 13228
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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.</p>
98 Authors
- Tanya J. Major
- Riku Takei
- Hirotaka Matsuo
- Megan P. Leask
- Nicholas A. Sumpter
- Ruth K. Topless
- Yuya Shirai
- Wei Wang
- Murray J. Cadzow
- Amanda J. Phipps-Green
- Zhiqiang Li
- Aichang Ji
- Marilyn E. Merriman
- Emily Morice
- Eric E. Kelley
- Wen-Hua Wei
- Sally P. A. McCormick
- Matthew J. Bixley
- Richard J. Reynolds
- Kenneth G. Saag
- Tayaza Fadason
- Evgenia Golovina
- Justin M. O'Sullivan
- Lisa K. Stamp
- Nicola Dalbeth
- Abhishek Abhishek
- Michael Doherty
- Edward Roddy
- Lennart T. H. Jacobsson
- Meliha C. Kapetanovic
- Olle Melander
- Mariano Andrés
- Fernando Pérez-Ruiz
- Rosa J. Torres
- Timothy Radstake
- Timothy L. Jansen
- Matthijs Janssen
- Leo A. B. Joosten
- Ruiqi Liu
- Orsolya I. Gaal
- Tania O. Crişan
- Simona Rednic
- Fina Kurreeman
- Tom W. J. Huizinga
- René Toes
- Frédéric Lioté
- Pascal Richette
- Thomas Bardin
- Hang Korng Ea
- Tristan Pascart
- Geraldine M. McCarthy
- Laura Helbert
- Blanka Stibůrková
- Anne-K. Tausche
- Till Uhlig
- Véronique Vitart
- Thibaud S. Boutin
- Caroline Hayward
- Philip L. Riches
- Stuart H. Ralston
- Archie Campbell
- Thomas M. MacDonald
- Akiyoshi Nakayama
- Tappei Takada
- Masahiro Nakatochi
- Seiko Shimizu
- Yusuke Kawamura
- Yu Toyoda
- Hirofumi Nakaoka
- Ken Yamamoto
- Keitaro Matsuo
- Nariyoshi Shinomiya
- Kimiyoshi Ichida
- Chaeyoung Lee
- Linda A. Bradbury
- Matthew A. Brown
- Philip C. Robinson
- Russell R. C. Buchanan
- Catherine L. Hill
- Susan Lester
- Malcolm D. Smith
- Maureen Rischmueller
- Hyon K. Choi
- Eli A. Stahl
- Jeff N. Miner
- Daniel H. Solomon
- Jing Cui
- Kathleen M. Giacomini
- Deanna J. Brackman
- Eric M. Jorgenson
- Hongbo Liu
- Katalin Susztak
- Suyash Shringarpure
- Alexander So
- Yukinori Okada
- Changgui Li
- Yongyong Shi
- Tony R. Merriman
1 Application
| Application ID | Title |
|---|---|
| 12611 | A genome-wide association study in gout: the NZ/Eurogout/US Consortium |
Enabling scientific discoveries that improve human health