Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals.

Commun Biol 2019 8;2:115. Epub 2019 Apr 8.

5Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, 359-8513 Japan.

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.

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http://dx.doi.org/10.1038/s42003-019-0339-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453927PMC
April 2019
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