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A genome-wide association analysis reveals new pathogenic pathways in gout
TJ. Major, R. Takei, H. Matsuo, MP. Leask, NA. Sumpter, RK. Topless, Y. Shirai, W. Wang, MJ. Cadzow, AJ. Phipps-Green, Z. Li, A. Ji, ME. Merriman, E. Morice, EE. Kelley, WH. Wei, SPA. McCormick, MJ. Bixley, RJ. Reynolds, KG. Saag, T. Fadason, E....
Language English Country United States
Document type Journal Article
NLK
ProQuest Central
from 2000-01-01 to 1 year ago
Health & Medicine (ProQuest)
from 2000-01-01 to 1 year ago
Public Health Database (ProQuest)
from 2000-01-01 to 1 year ago
- MeSH
- Genome-Wide Association Study * MeSH
- Gout * genetics MeSH
- Genetic Predisposition to Disease * MeSH
- Hyperuricemia genetics MeSH
- Polymorphism, Single Nucleotide * MeSH
- Uric Acid * MeSH
- Humans MeSH
- Mendelian Randomization Analysis MeSH
- NLR Family, Pyrin Domain-Containing 3 Protein genetics MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
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.
Academic Rheumatology School of Medicine University of Nottingham Nottingham United Kingdom
Australian Parkinsons Mission Garvan Institute of Medical Research Sydney New South Wales Australia
Center for Biomedical Network Research on Rare Diseases ISCIII Madrid Spain
Center for Treatment of Rheumatic and Musculoskeletal Diseases Diakonhjemmet Hospital Oslo Norway
Department of Biochemistry Hospital La Paz Institute for Health Research Madrid Spain
Department of Biochemistry University of Otago Dunedin New Zealand
Department of Bioinformatics and Life Science Soongsil University Seoul South Korea
Department of Cancer Genome Research Sasaki Institute Sasaki Foundation Tokyo Japan
Department of Clinical Medicine Miguel Hernandez University Alicante Spain
Department of Clinical Sciences Lund University Malmö Sweden
Department of Emergency and Internal Medicine Skåne University Hospital Malmö Sweden
Department of Genome Informatics Graduate School of Medicine The University of Tokyo Tokyo Japan
Department of Medical Biochemistry Kurume University School of Medicine Fukuoka Japan
Department of Medicine University of Auckland Auckland New Zealand
Department of Medicine University of Otago Christchurch Christchurch New Zealand
Department of Microbiology and Immunology University of Otago Dunedin New Zealand
Department of Pathophysiology Tokyo University of Pharmacy and Life Sciences Tokyo Japan
Department of Pharmacy The University of Tokyo Hospital Tokyo Japan
Department of Physiology and Pharmacology West Virginia University Morgantown WV USA
Department of Rheumatology and Clinical Immunology University Medical Center Utrecht The Netherlands
Department of Rheumatology Austin Hospital Melbourne Victoria Australia
Department of Rheumatology Hopital Saint Philibert Lille Catholic University Lille France
Department of Rheumatology Leiden University Medical Center Leiden The Netherlands
Department of Rheumatology VieCuri Medical Centre Venlo The Netherlands
Department of Statistical Genetics Osaka University Graduate School of Medicine Osaka Japan
Department of Women's and Children's Health University of Otago Dunedin New Zealand
Discipline of Medicine University of Adelaide Adelaide Australia
Division of Cancer Epidemiology and Prevention Aichi Cancer Center Aichi Japan
Division of Cancer Epidemiology Nagoya University Graduate School of Medicine Aichi Japan
Division of Research Kaiser Permanente Northern California Oakland CA USA
Division of Rheumatology Brigham and Women's Hospital Harvard Medical School Boston MA USA
Flinders University Adelaide South Australia Australia
Genomics R and D 23andMe Inc Sunnyvale CA USA
Institute of Rheumatology Prague Czech Republic
Laboratory for Systems Genetics RIKEN Center for Integrative Medical Sciences Yokohama Japan
Liggins Institute University of Auckland Auckland New Zealand
MRC Lifecourse Epidemiology Unit University of Southampton Southampton United Kingdom
Rheumatology Department Dr Balmis General University Hospital ISABIAL Alicante Spain
Rheumatology Department Feel'Gout GH Paris Saint Joseph Paris France
Rheumatology Department The Queen Elizabeth Hospital Woodville South South Australia Australia
School of Clinical Medicine Faculty of Medicine University of Queensland Brisbane Australia
School of Medicine Keele University Keele Staffordshire United Kingdom
Service of Rheumatology Center Hospitalier Universitaire Vaudois Lausanne Switzerland
The Institute of Metabolic Diseases Qingdao University Qingdao Shandong China
The Japan Multi Institutional Collaborative Cohort Study Tokyo Japan
University of Lausanne Lausanne Switzerland
Viscient Biosciences 5752 Oberlin Dr Suite 111 San Diego CA 92121 USA
References provided by Crossref.org
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- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2024 $b 56 $c 11 $d 2392-2406 $e 20241015 $i 1546-1718 $m Nature genetics $n Nat Genet $x MED00003458
- LZP __
- $a Pubmed-20250121
