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

• Published in: Communications biology Vol. 2; no. 1; p. 115
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.04.2019; Nature Publishing Group
• Subjects: 45; 45/43; 631/208/205/2138; 692/699/1670/3/2765/1528; Alleles; Arthritis; Biology; Biomedical and Life Sciences; Computational Biology; Gene loci; Gene regulation; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomes; Genotype; Gout; Gout - blood; Gout - etiology; Gout - metabolism; Hepatocyte nuclear factor 4; Humans; Hyperuricemia; Japan; Life Sciences; Meta-analysis; Molecular Sequence Annotation; Oxidative metabolism; Oxidative stress; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Quantitative Trait, Heritable; Rheumatism; Uric acid; Uric Acid - blood; Japan
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-019-0339-0

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. Masahiro Nakatochi et al. report a genome-wide meta-analysis of serum uric acid levels in the Japanese population. They identify 36 loci, including eight previously unreported loci, suggesting key cellular processes that contribute to elevated serum uric acid levels, which can lead to gout.