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

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 (<i>P</i><5 × 10^-8) including eight novel loci. Of these, missense variants of <i>SESN2</i> and <i>PNPLA3</i> were predicted to be damaging to the function of these proteins; another five loci-<i>TMEM18</i>, <i>TM4SF4</i>, <i>MXD3-LMAN2</i>, <i>PSORS1C1-PSORS1C2</i>, and <i>HNF4A</i>-are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, <i>LINC01578</i>, 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.