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

Masahiro Nakatochi, Masahiro Kanai, Akiyoshi Nakayama, Asahi Hishida, Yusuke Kawamura, Sahoko Ichihara, Masato Akiyama, Hiroaki Ikezaki, Norihiro Furusyo, Seiko Shimizu, Ken Yamamoto, Makoto Hirata, Rieko Okada, Sayo Kawai, Makoto Kawaguchi, Yuichiro Nishida, Chisato Shimanoe, Rie Ibusuki, Toshiro Takezaki, Mayuko NakajimaMikiya Takao, Etsuko Ozaki, Daisuke Matsui, Takeshi Nishiyama, Sadao Suzuki, Naoyuki Takashima, Yoshikuni Kita, Kaori Endoh, Kiyonori Kuriki, Hirokazu Uemura, Kokichi Arisawa, Isao Oze, Keitaro Matsuo, Yohko Nakamura, Haruo Mikami, Takashi Tamura, Hiroshi Nakashima, Takahiro Nakamura, Norihiro Kato, Koichi Matsuda, Yoshinori Murakami, Tatsuaki Matsubara, Mariko Naito, Michiaki Kubo, Yoichiro Kamatani, Nariyoshi Shinomiya, Mitsuhiro Yokota, Kenji Wakai, Yukinori Okada, Hirotaka Matsuo

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

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.

Original languageEnglish
Article number115
JournalCommunications Biology
Volume2
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint

Dive into the research topics of 'Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals'. Together they form a unique fingerprint.

Cite this