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

Commun Biol. 2019 Apr 8;2:115. doi: 10.1038/s42003-019-0339-0. eCollection 2019.

Abstract

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

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Computational Biology
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Genotype
  • Gout / blood
  • Gout / etiology
  • Gout / metabolism
  • Humans
  • Japan
  • Molecular Sequence Annotation
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci*
  • Quantitative Trait, Heritable*
  • Uric Acid / blood*

Substances

  • Uric Acid