Tin, A. et al. Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels. Nat. Genet. 51, 1459–1474 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martinon, F. et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440, 237–241 (2006).

Article  CAS  PubMed  Google Scholar 

Joosten, L. A. et al. Engagement of fatty acids with Toll-like receptor 2 drives interleukin-1β production via the ASC/caspase 1 pathway in monosodium urate monohydrate crystal-induced gouty arthritis. Arthritis Rheumatol. 62, 3237–3248 (2010).

Article  CAS  Google Scholar 

Badii, M., Gaal, O., Popp, R. A., Crișan, T. O. & Joosten, L. A. Trained immunity and inflammation in rheumatic diseases. Joint Bone Spine 89, 105364 (2022).

Article  CAS  PubMed  Google Scholar 

Chhana, A., Lee, G. & Dalbeth, N. Factors influencing the crystallization of monosodium urate: a systematic literature review. BMC Musculoskelet. Disord. 16, 296 (2015).

Article  PubMed  PubMed Central  Google Scholar 

Loeb, J. N. The influence of temperature on the solubility of monosodium urate. Arthritis Rheumatol. 15, 189–192 (1972).

Article  CAS  Google Scholar 

Allen, D. J., Milosovich, G. & Mattocks, A. M. Inhibition of monosodium urate needle crystal growth. Arthritis Rheumatol. 8, 1123–1133 (1965).

Article  CAS  Google Scholar 

Elsaid, K. et al. Amplification of inflammation by lubricin deficiency implicated in incident, erosive gout independent of hyperuricemia. Arthritis Rheumatol. 75, 794–805 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mandal, A. K. & Mount, D. B. The molecular physiology of uric acid homeostasis. Ann. Rev. Physiol. 77, 323–345 (2015).

Article  CAS  Google Scholar 

Köttgen, A. et al. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat. Genet. 45, 145–154 (2013).

Article  PubMed  Google Scholar 

Ichida, K. et al. Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat. Commun. 3, 764 (2012).

Article  PubMed  Google Scholar 

Uffelmann, E. et al. Genome-wide association studies. Nat. Rev. Methods Prim. 1, 59 (2021).

Article  CAS  Google Scholar 

Li, S. et al. The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts. PLoS Genet. 3, e194 (2007).

Article  PubMed  PubMed Central  Google Scholar 

Nakatochi, M. et al. Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals. Commun. Biol. 2, 115 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Zhou, W. et al. Global biobank meta-analysis initiative: powering genetic discovery across human disease. Cell Genom. 2, 100192 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Major, T. J. et al. A genome-wide association analysis of 2,622,830 individuals reveals new pathogenic pathways in gout. Preprint at medRxiv https://doi.org/10.1101/2022.11.26.22281768 (2022).

Sinnott-Armstrong, N., Naqvi, S., Rivas, M. & Pritchard, J. K. GWAS of three molecular traits highlights core genes and pathways alongside a highly polygenic background. Elife 10, e58615 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wuttke, M. et al. Imputation-powered whole-exome analysis identifies genes associated with kidney function and disease in the UK Biobank. Nat. Commun. 14, 1287 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Scholz, M. et al. X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements. Nat. Commun. 18, 586 (2024).

Article  Google Scholar 

Cho, C. et al. Large-scale cross-ancestry genome-wide meta-analysis of serum urate. Nat. Commun. 15, 3441 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

McCormick, N. et al. Assessing the causal relationships between insulin resistance and hyperuricemia and gout using bidirectional Mendelian randomization. Arthritis Rheumatol. 73, 2096–2104 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rasheed, H., Hughes, K., Flynn, T. J. & Merriman, T. R. Mendelian randomization provides no evidence for a causal role of serum urate in increasing serum triglyceride levels. Circ. Cardiovasc. Genet. 7, 830–837 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lyngdoh, T. et al. Serum uric acid and adiposity: deciphering causality using a bidirectional Mendelian randomization approach. PLoS One 7, e39321 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zamudio-Cuevas, Y. et al. Phagocytosis of monosodium urate crystals by human synoviocytes induces inflammation. Exp. Biol. Med. 244, 344–351 (2019).

Article  CAS  Google Scholar 

Kirby, A. et al. Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing. Nat. Genet. 45, 299–303 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kraus, M. R. C. et al. Two mutations in human BICC1 resulting in Wnt pathway hyperactivity associated with cystic renal syndrome. Hum. Mutat. 33, 86–90 (2012).

Article  CAS  PubMed  Google Scholar 

Hart, T. C. et al. Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy. J. Med. Genet. 39, 882–892 (2002).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Boyle, E. A., Li, Y. I. & Pritchard, J. K. An expanded view of complex traits: from polygenic to omnigenic. Cell 169, 1177–1186 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu, X., Li, Y. I. & Pritchard, J. K. Trans effects on gene expression can drive omnigenic inheritance. Cell 177, 1022–1034 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ketharnathan, S. et al. A non-coding genetic variant maximally associated with serum urate levels is functionally linked to HNF4A-dependent PDZK1 expression. Hum. Mol. Genet. 27, 3964–3973 (2018).

CAS  PubMed  Google Scholar 

Leask, M. P. et al. Functional urate-associated genetic variants influence expression of lincRNAs LINC01229 and MAFTRR. Front. Genet. 9, 733 (2018).

Article  CAS  PubMed  Google Scholar 

Boocock, J. et al. Genomic dissection of 43 serum urate-associated loci provides multiple insights into molecular mechanisms of urate control. Hum. Mol. Genet. 29, 923–943 (2020).

Article  CAS  PubMed