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 language | English |
|---|---|
| Article number | 115 |
| Journal | Communications Biology |
| Volume | 2 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Dec 1 2019 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
- Medicine (miscellaneous)
Cite this
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.
In: Communications Biology, Vol. 2, No. 1, 115, 01.12.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals
AU - Nakatochi, Masahiro
AU - Kanai, Masahiro
AU - Nakayama, Akiyoshi
AU - Hishida, Asahi
AU - Kawamura, Yusuke
AU - Ichihara, Sahoko
AU - Akiyama, Masato
AU - Ikezaki, Hiroaki
AU - Furusyo, Norihiro
AU - Shimizu, Seiko
AU - Yamamoto, Ken
AU - Hirata, Makoto
AU - Okada, Rieko
AU - Kawai, Sayo
AU - Kawaguchi, Makoto
AU - Nishida, Yuichiro
AU - Shimanoe, Chisato
AU - Ibusuki, Rie
AU - Takezaki, Toshiro
AU - Nakajima, Mayuko
AU - Takao, Mikiya
AU - Ozaki, Etsuko
AU - Matsui, Daisuke
AU - Nishiyama, Takeshi
AU - Suzuki, Sadao
AU - Takashima, Naoyuki
AU - Kita, Yoshikuni
AU - Endoh, Kaori
AU - Kuriki, Kiyonori
AU - Uemura, Hirokazu
AU - Arisawa, Kokichi
AU - Oze, Isao
AU - Matsuo, Keitaro
AU - Nakamura, Yohko
AU - Mikami, Haruo
AU - Tamura, Takashi
AU - Nakashima, Hiroshi
AU - Nakamura, Takahiro
AU - Kato, Norihiro
AU - Matsuda, Koichi
AU - Murakami, Yoshinori
AU - Matsubara, Tatsuaki
AU - Naito, Mariko
AU - Kubo, Michiaki
AU - Kamatani, Yoichiro
AU - Shinomiya, Nariyoshi
AU - Yokota, Mitsuhiro
AU - Wakai, Kenji
AU - Okada, Yukinori
AU - Matsuo, Hirotaka
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85068744369&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068744369&partnerID=8YFLogxK
U2 - 10.1038/s42003-019-0339-0
DO - 10.1038/s42003-019-0339-0
M3 - Article
AN - SCOPUS:85068744369
VL - 2
JO - Communications Biology
JF - Communications Biology
SN - 2399-3642
IS - 1
M1 - 115
ER -