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

• Nakatochi, Masahiro

• Kanai, Masahiro

• Nakayama, Akiyoshi

• Hishida, Asahi

• Kawamura, Yusuke

• Ichihara, Sahoko

• Akiyama, Masato

• Ikezaki, Hiroaki

• Furusyo, Norihiro

• Shimizu, Seiko

• Yamamoto, Ken

• Hirata, Makoto

• Okada, Rieko

• Kawai, Sayo

• Kawaguchi, Makoto

• Nishida, Yuichiro

• Shimanoe, Chisato

• Ibusuki, Rie

• Takezaki, Toshiro

• Nakajima, Mayuko

• Takao, Mikiya

• Ozaki, Etsuko

• Matsui, Daisuke

• Nishiyama, Takeshi

• Suzuki, Sadao

• Takashima, Naoyuki

• Kita, Yoshikuni

• Endoh, Kaori

• Kuriki, Kiyonori

• Uemura, Hirokazu

• Arisawa, Kokichi

• Oze, Isao

• Matsuo, Keitaro

• Nakamura, Yohko

• Mikami, Haruo

• Tamura, Takashi

• Nakashima, Hiroshi

• Nakamura, Takahiro

• Kato, Norihiro

• Matsuda, Koichi

• Murakami, Yoshinori

• Matsubara, Tatsuaki

• Naito, Mariko

• Kubo, Michiaki

• Kamatani, Yoichiro

• Shinomiya, Nariyoshi

• Yokota, Mitsuhiro

• Wakai, Kenji

• Okada, Yukinori

• Matsuo, Hirotaka

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.

Journal

• Communications Biology

  Communications Biology 2 115-, 2019-04-08

  Springer Nature

Keywords

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

Details

• CRID: 1050004953596694144
• NII Article ID: 120006937615
• ISSN: 23993642
• DOI: 10.1038/s42003-019-0339-0
• Web Site: http://repo.lib.tokushima-u.ac.jp/115068
• Web Site: https://www.nature.com/articles/s42003-019-0339-0.pdf
• Web Site: https://www.nature.com/articles/s42003-019-0339-0
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN