A genome-wide association analysis reveals new pathogenic pathways in gout*
Major, T.J. ; Kapetanovic, M.C. LU ; Melander, O. LU
and Merriman, T.R.
(2024)
In Nature Genetics
56(11).
- 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... (More)
- 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. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/32d691ca-7d7f-4e8f-8649-3a8af8415bcb
- author
- Major, T.J.
; Kapetanovic, M.C.
LU
; Melander, O.
LU
and Merriman, T.R.
- author collaboration
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Genetics
- volume
- 56
- issue
- 11
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85206813683
- pmid:39406924
- ISSN
- 1061-4036
- DOI
- 10.1038/s41588-024-01921-5
- language
- English
- LU publication?
- yes
- id
- 32d691ca-7d7f-4e8f-8649-3a8af8415bcb
- date added to LUP
- 2025-09-25 08:29:19
- date last changed
- 2025-09-26 03:03:18
@article{32d691ca-7d7f-4e8f-8649-3a8af8415bcb,
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. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.}},
author = {{Major, T.J. and Kapetanovic, M.C. and Melander, O. and Merriman, T.R.}},
issn = {{1061-4036}},
language = {{eng}},
number = {{11}},
publisher = {{Nature Publishing Group}},
series = {{Nature Genetics}},
title = {{A genome-wide association analysis reveals new pathogenic pathways in gout*}},
url = {{http://dx.doi.org/10.1038/s41588-024-01921-5}},
doi = {{10.1038/s41588-024-01921-5}},
volume = {{56}},
year = {{2024}},
}