1Data Science Division, Data Coordinating Center, Department of Advanced Medicine, Nagoya University Hospital, Nagoya, 466-8560 Japan.
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045 Japan.
Commun Biol. 2019 Apr 8;2:115. doi: 10.1038/s42003-019-0339-0. eCollection 2019.
Gout is a common arthritis caused by elevated serum uric acid (SUA) levels. Here we investigated loci influencing SUA in a genome-wide meta-analysis with 121,745 Japanese subjects. We identified 8948 variants at 36 genomic loci (<5 × 10) including eight novel loci. Of these, missense variants of and were predicted to be damaging to the function of these proteins; another five loci-, , , , and -are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, , is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout.
痛风是一种由血清尿酸（SUA）水平升高引起的常见关节炎。在这里，我们对 121745 名日本受试者进行了全基因组荟萃分析，研究了影响 SUA 的基因座。我们在 36 个基因组座中鉴定出了 8948 个变体（<5×10），包括 8 个新的基因座。其中， 和 中的错义变体被预测对这些蛋白质的功能有损害；另外五个基因座-、-、-、-和-与细胞代谢、增殖或氧化应激有关；而剩余的基因座-则未知。我们还鉴定了 132 个与 SUA 升高等位基因相关的表达水平相关的相关基因。这些基因在 UniProt 运输术语中富集，表明与运输相关的基因在 SUA 调节中的重要性。此外，通过我们自己的荟萃分析和全球尿酸遗传学联合会的跨种族荟萃分析，发现了 15 个与 SUA 相关的更多新基因座。我们的研究结果为高尿酸血症/痛风的发病机制、治疗和预防提供了新的见解。
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