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Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals
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 variant...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2019
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453927/ https://www.ncbi.nlm.nih.gov/pubmed/30993211 http://dx.doi.org/10.1038/s42003-019-0339-0 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Nakatochi, Masahiro |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-6453927 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2019 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-64539272019-04-16 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 Commun Biol Article 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. Nature Publishing Group UK 2019-04-08 /pmc/articles/PMC6453927/ /pubmed/30993211 http://dx.doi.org/10.1038/s42003-019-0339-0 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article 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 Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals |
| title | Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals |
| title_full | Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals |
| title_fullStr | Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals |
| title_full_unstemmed | Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals |
| title_short | Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals |
| title_sort | genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in japanese individuals |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453927/ https://www.ncbi.nlm.nih.gov/pubmed/30993211 http://dx.doi.org/10.1038/s42003-019-0339-0 |
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