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Commun Biol. 2019 Apr 8;2:115. doi: 10.1038/s42003-019-0339-0. eCollection 2019.

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

Author information

1
1Data Science Division, Data Coordinating Center, Department of Advanced Medicine, Nagoya University Hospital, Nagoya, 466-8560 Japan.
2
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045 Japan.
3
3Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, 565-0871 Japan.
4
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115 USA.
5
5Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, 359-8513 Japan.
6
Medical Squadron, Air Base Group, Western Aircraft Control and Warning Wing, Japan Air Self-Defense Force, Kasuga, 816-0804 Japan.
7
7Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, 466-8550 Japan.
8
8Department of General Medicine, National Defense Medical College, Tokorozawa, 359-8513 Japan.
9
9Department of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke, 329-0498 Japan.
10
10Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582 Japan.
11
11Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, 812-8582 Japan.
12
12Department of Medical Biochemistry, Kurume University School of Medicine, Kurume, 830-0011 Japan.
13
13Laboratory of Genome Technology, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639 Japan.
14
14Department of Urology, National Defense Medical College, Tokorozawa, 359-8513 Japan.
15
15Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, 849-8501 Japan.
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16International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544 Japan.
17
17Department of Surgery, National Defense Medical College, Tokorozawa, 359-8513 Japan.
18
18Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, 602-8566 Japan.
19
19Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8602 Japan.
20
20Department of Health Science, Shiga University of Medical Science, Otsu, 520-2192 Japan.
21
21Department of Nursing, Tsuruga City College of Nursing, Fukui, 914-8501 Japan.
22
22Laboratory of Public Health, Division of Nutritional Sciences, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, 422-8526 Japan.
23
23Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503 Japan.
24
24Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, 464-8681 Japan.
25
25Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550 Japan.
26
26Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba, 260-8717 Japan.
27
27Department of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa, 359-8513 Japan.
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28Laboratory for Mathematics, National Defense Medical College, Tokorozawa, 359-8513 Japan.
29
29Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, 162-8655 Japan.
30
30Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, 108-8639 Japan.
31
31Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639 Japan.
32
32Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, 464-8651 Japan.
33
33Department of Oral Epidemiology, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, 734-8553 Japan.
34
RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045 Japan.
35
35Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, 606-8507 Japan.
36
36Department of Genome Science, School of Dentistry, Aichi Gakuin University, Nagoya, 464-8651 Japan.
37
37Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, 565-0871 Japan.
#
Contributed equally

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.

Conflict of interest statement

The authors declare no competing interests.

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