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

被引：78

作者：

Nakatochi, Masahiro ^{[1
]}

Kanai, Masahiro ^{[2
,3
,4
]}

Nakayama, Akiyoshi ^{[5
,6
]}

Hishida, Asahi ^{[7
]}

Kawamura, Yusuke ^{[5
,8
]}

Ichihara, Sahoko ^{[9
]}

Akiyama, Masato ^{[2
,10
]}

Ikezaki, Hiroaki ^{[11
]}

Furusyo, Norihiro ^{[11
]}

Shimizu, Seiko ^{[5
]}

Yamamoto, Ken ^{[12
]}

Hirata, Makoto ^{[13
]}

Okada, Rieko ^{[7
]}

Kawai, Sayo ^{[7
]}

Kawaguchi, Makoto ^{[5
,14
]}

Nishida, Yuichiro ^{[15
]}

Shimanoe, Chisato ^{[15
]}

Ibusuki, Rie ^{[16
]}

Takezaki, Toshiro ^{[16
]}

Nakajima, Mayuko ^{[5
]}

Takao, Mikiya ^{[5
,17
]}

Ozaki, Etsuko ^{[18
]}

Matsui, Daisuke ^{[18
]}

Nishiyama, Takeshi ^{[19
]}

Suzuki, Sadao ^{[19
]}

Takashima, Naoyuki ^{[20
]}

Kita, Yoshikuni ^{[21
]}

Endoh, Kaori ^{[22
]}

Kuriki, Kiyonori ^{[22
]}

Uemura, Hirokazu ^{[23
]}

Arisawa, Kokichi ^{[23
]}

Oze, Isao ^{[24
]}

Matsuo, Keitaro ^{[24
,25
]}

Nakamura, Yohko ^{[26
]}

Mikami, Haruo ^{[26
]}

Tamura, Takashi ^{[7
]}

Nakashima, Hiroshi ^{[27
]}

Nakamura, Takahiro ^{[28
]}

Kato, Norihiro ^{[29
]}

Matsuda, Koichi ^{[30
]}

Murakami, Yoshinori ^{[31
]}

Matsubara, Tatsuaki ^{[32
]}

Naito, Mariko ^{[7
,33
]}

Kubo, Michiaki ^{[34
]}

Kamatani, Yoichiro ^{[2
,35
]}

Shinomiya, Nariyoshi ^{[5
]}

Yokota, Mitsuhiro ^{[36
]}

Wakai, Kenji ^{[7
]}

Okada, Yukinori ^{[2
,3
,37
]}

Matsuo, Hirotaka ^{[5
]}

机构：

[1] Nagoya Univ Hosp, Data Sci Div, Dept Adv Med, Data Coordinating Ctr, Nagoya, Aichi 4668560, Japan

[2] RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa 2300045, Japan

[3] Osaka Univ, Grad Sch Med, Dept Stat Genet, Suita, Osaka 5650871, Japan

[4] Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA

[5] Natl Def Med Coll, Dept Integrat Physiol & Bionano Med, Tokorozawa, Saitama 3598513, Japan

[6] Japan Air Self Def Force, Western Aircraft Control & Warning Wing, Air Base Grp, Med Squadron, Kasuga, Fukuoka 8160804, Japan

[7] Nagoya Univ, Dept Prevent Med, Grad Sch Med, Nagoya, Aichi 4668550, Japan

[8] Natl Def Med Coll, Dept Gen Med, Tokorozawa, Saitama 3598513, Japan

[9] Jichi Med Univ, Dept Environm & Prevent Med, Sch Med, Shimotsuke 3290498, Japan

[10] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Fukuoka 8128582, Japan

[11] Kyushu Univ Hosp, Dept Gen Internal Med, Fukuoka, Fukuoka 8128582, Japan

[12] Kurume Univ, Dept Med Biochem, Sch Med, Kurume, Fukuoka 8300011, Japan

[13] Univ Tokyo, Inst Med Sci, Lab Genome Technol, Tokyo 1088639, Japan

[14] Natl Def Med Coll, Dept Urol, Tokorozawa, Saitama 3598513, Japan

[15] Saga Univ, Dept Prevent Med, Fac Med, Saga 8498501, Japan

[16] Kagoshima Univ, Grad Sch Med & Dent Sci, Int Isl & Community Med, Kagoshima 8908544, Japan

[17] Natl Def Med Coll, Dept Surg, Tokorozawa, Saitama 3598513, Japan

[18] Kyoto Prefectural Univ Med, Dept Epidemiol Community Hlth & Med, Kyoto 6028566, Japan

[19] Nagoya City Univ, Dept Publ Hlth, Grad Sch Med Sci, Nagoya, Aichi 4678602, Japan

[20] Shiga Univ Med Sci, Dept Hlth Sci, Otsu, Shiga 5202192, Japan

[21] Tsuruga City Coll Nursing, Dept Nursing, Fukui 9148501, Japan

[22] Univ Shizuoka, Sch Food & Nutr Sci, Div Nutr Sci, Lab Publ Hlth, Shizuoka 4228526, Japan

[23] Tokushima Univ, Inst Biomed Sci, Dept Prevent Med, Grad Sch, Tokushima 7708503, Japan

[24] Aichi Canc Ctr, Div Canc Epidemiol & Prevent, Res Inst, Nagoya, Aichi 4648681, Japan

[25] Nagoya Univ, Dept Epidemiol, Grad Sch Med, Nagoya, Aichi 4668550, Japan

[26] Chiba Canc Ctr, Canc Prevent Ctr, Res Inst, Chiba 2608717, Japan

[27] Natl Def Med Coll, Dept Prevent Med & Publ Hlth, Tokorozawa, Saitama 3598513, Japan

[28] Natl Def Med Coll, Lab Math, Tokorozawa, Saitama 3598513, Japan

[29] Natl Ctr Global Hlth & Med, Res Inst, Dept Gene Diagnost & Therapeut, Tokyo 1628655, Japan

[30] Univ Tokyo, Grad Sch Frontier Sci, Dept Computat Biol & Med Sci, Tokyo 1088639, Japan

[31] Univ Tokyo, Inst Med Sci, Div Mol Pathol, Tokyo 1088639, Japan

[32] Aichi Gakuin Univ, Sch Dent, Dept Internal Med, Nagoya, Aichi 4648651, Japan

[33] Hiroshima Univ, Dept Oral Epidemiol, Grad Sch Biomed & Hlth Sci, Hiroshima 7348553, Japan

[34] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa 2300045, Japan

[35] Kyoto Univ, Ctr Genom Med, Grad Sch Med, Kyoto 6068507, Japan

[36] Aichi Gakuin Univ, Sch Dent, Dept Genome Sci, Nagoya, Aichi 4648651, Japan

[37] Osaka Univ, Lab Stat Immunol, Immunol Frontier Res Ctr WPI IFReC, Suita, Osaka 5650871, Japan

来源：

COMMUNICATIONS BIOLOGY | 2019年 / 2卷 / 1期

基金：

日本学术振兴会;

关键词：

MULTIINSTITUTIONAL COLLABORATIVE COHORT; URATE TRANSPORTER; SUSCEPTIBILITY LOCI; GENETIC-LOCI; GOUT; RISK; HYPERURICEMIA; VARIANT; DISEASE; POLYMORPHISMS;

D O I：

10.1038/s42003-019-0339-0

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

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 x 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

页数：10

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