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

被引：0

作者：

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 Nakajima

Mikiya 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

机构：

[1] Nagoya University Hospital,Data Science Division, Data Coordinating Center, Department of Advanced Medicine

[2] RIKEN Center for Integrative Medical Sciences,Laboratory for Statistical Analysis

[3] Osaka University Graduate School of Medicine,Department of Statistical Genetics

[4] Harvard Medical School,Department of Biomedical Informatics

[5] National Defense Medical College,Department of Integrative Physiology and Bio

[6] Western Aircraft Control and Warning Wing,Nano Medicine

[7] Japan Air Self-Defense Force,Medical Squadron, Air Base Group

[8] Nagoya University Graduate School of Medicine,Department of Preventive Medicine

[9] National Defense Medical College,Department of General Medicine

[10] Jichi Medical University School of Medicine,Department of Environmental and Preventive Medicine

[11] Kyushu University,Department of Ophthalmology, Graduate School of Medical Sciences

[12] Kyushu University Hospital,Department of General Internal Medicine

[13] Kurume University School of Medicine,Department of Medical Biochemistry

[14] The University of Tokyo,Laboratory of Genome Technology, Institute of Medical Science

[15] National Defense Medical College,Department of Urology

[16] Saga University,Department of Preventive Medicine, Faculty of Medicine

[17] Kagoshima University Graduate School of Medical and Dental Sciences,International Island and Community Medicine

[18] National Defense Medical College,Department of Surgery

[19] Kyoto Prefectural University of Medicine,Department of Epidemiology for Community Health and Medicine

[20] Nagoya City University Graduate School of Medical Sciences,Department of Public Health

[21] Shiga University of Medical Science,Department of Health Science

[22] Tsuruga City College of Nursing,Department of Nursing

[23] University of Shizuoka,Laboratory of Public Health, Division of Nutritional Sciences, School of Food and Nutritional Sciences

[24] Tokushima University Graduate School,Department of Preventive Medicine, Institute of Biomedical Sciences

[25] Aichi Cancer Center Research Institute,Division of Cancer Epidemiology and Prevention

[26] Nagoya University Graduate School of Medicine,Department of Epidemiology

[27] Chiba Cancer Center Research Institute,Cancer Prevention Center

[28] National Defense Medical College,Department of Preventive Medicine and Public Health

[29] National Defense Medical College,Laboratory for Mathematics

[30] Research Institute,Department of Gene Diagnostics and Therapeutics

[31] National Center for Global Health and Medicine,Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences

[32] The University of Tokyo,Division of Molecular Pathology

[33] Institute of Medical Science,Department of Internal Medicine, School of Dentistry

[34] The University of Tokyo,Department of Oral Epidemiology

[35] Aichi Gakuin University,Center for Genomic Medicine

[36] Hiroshima University Graduate School of Biomedical & Health Sciences,Department of Genome Science, School of Dentistry

[37] RIKEN Center for Integrative Medical Sciences,Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI

[38] Kyoto University Graduate School of Medicine,IFReC)

[39] Aichi Gakuin University,undefined

[40] Osaka University,undefined

来源：

Communications Biology | / 2卷

关键词：

D O I：

暂无

中图分类号：

学科分类号：

摘要：

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.

引用

共 50 条

[1] 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
COMMUNICATIONS BIOLOGY, 2019, 2 (1)
[2] GENOME-WIDE META-ANALYSIS REVEALED MULTIPLE NOVEL LOCI ASSOCIATED WITH SERUM URIC ACIDLEVELS IN JAPANESE
Matsuo, Hirotaka
Nakatochi, Masahiro
Kanai, Masahiro
Nakayama, Akiyoshi
Hishida, Asahi
Kawamura, Yusuke
Nakajima, Mayuko
Kamatani, Yoichiro
Shinomiya, Nariyoshi
Yokota, Mitsuhiro
Wakai, Kenji
Okada, Yukinori
ANNALS OF THE RHEUMATIC DISEASES, 2019, 78 : 95 - 95
[3] Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci
Patsopoulos, Nikolaos A.
de Bakker, Paul I. W.
ANNALS OF NEUROLOGY, 2011, 70 (06) : 897 - 912
[4] Genome-wide meta-analysis identifies 3 novel loci associated with stroke
Malik, Rainer
Rannikmaee, Kristiina
Traylor, Matthew
Georgakis, Marios K.
Sargurupremraj, Muralidharan
Markus, Hugh S.
Hopewell, Jemma C.
Debette, Stephanie
Sudlow, Cathie L. M.
Dichgans, Martin
ANNALS OF NEUROLOGY, 2018, 84 (06) : 934 - 939
[5] Refining genome-wide associated loci for serum uric acid in individuals with African ancestry
Chen, Guanjie
Shriner, Daniel
Doumatey, Ayo P.
Zhou, Jie
Bentley, Amy R.
Lei, Lin
Adeyemo, Adebowale
Rotimi, Charles N.
HUMAN MOLECULAR GENETICS, 2020, 29 (03) : 506 - 514
[6] Genome-wide meta-analysis identifies novel loci associated with parathyroid hormone level
Antonela Matana
Dubravka Brdar
Vesela Torlak
Thibaud Boutin
Marijana Popović
Ivana Gunjača
Ivana Kolčić
Vesna Boraska Perica
Ante Punda
Ozren Polašek
Maja Barbalić
Caroline Hayward
Tatijana Zemunik
Molecular Medicine, 2018, 24
[7] Genome-wide meta-analysis identifies novel loci associated with parathyroid hormone level
Matana, Antonela
Brdar, Dubravka
Torlak, Vesela
Boutin, Thibaud
Popovic, Marijana
Gunjaca, Ivana
Kolcic, Ivana
Perica, Vesna Boraska
Punda, Ante
Polasek, Ozren
Barbalic, Maja
Hayward, Caroline
Zemunik, Tatijana
MOLECULAR MEDICINE, 2018, 24
[8] A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder
Wang, Ke-Sheng
Liu, Xue-Feng
Aragam, Nagesh
SCHIZOPHRENIA RESEARCH, 2010, 124 (1-3) : 192 - 199
[9] Genome-wide association meta-analysis identifies six loci for osteocalcin levels
Hsu, Yi-Hsiang
Karasik, David
Kiel, Douglas P.
Teumer, Alexander
Trajanoska, Katerina
Rivadeneira, Fernando
JOURNAL OF BONE AND MINERAL RESEARCH, 2019, 34 : 78 - 79
[10] Genome-wide association meta-analysis identifies two novel loci associated with dental caries
Nogawa, Shun
Morishita, Satoru
Saito, Kenji
Kato, Hisanori
BMC ORAL HEALTH, 2024, 24 (01):

← 1 2 3 4 5 →