title: Genome-wide association analysis identifies three new risk loci for gout arthritis in Han Chinese.
abstract: Gout is one of the most common types of inflammatory arthritis, caused by the deposition of monosodium urate crystals in and around the joints. Previous genome-wide association studies (GWASs) have identified many genetic loci associated with raised serum urate concentrations. However, hyperuricemia alone is not sufficient for the development of gout arthritis. Here we conduct a multistage GWAS in Han Chinese using 4,275 male gout patients and 6,272 normal male controls (1,255 cases and 1,848 controls were genome-wide genotyped), with an additional 1,644 hyperuricemic controls. We discover three new risk loci, 17q23.2 (rs11653176, P=1.36 × 10(-13), BCAS3), 9p24.2 (rs12236871, P=1.48 × 10(-10), RFX3) and 11p15.5 (rs179785, P=1.28 × 10(-8), KCNQ1), which contain inflammatory candidate genes. Our results suggest that these loci are most likely related to the progression from hyperuricemia to inflammatory gout, which will provide new insights into the pathogenesis of gout arthritis.
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Changgui
authors.initials: C
authors.lastname: Li
authors.affiliation: 1] Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China [2] Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Shiguo
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authors.lastname: Liu
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Can
authors.initials: C
authors.lastname: Wang
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Han
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Lingling
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authors.lastname: Cui
authors.affiliation: Department of Rheumatology and Immunology of the Affiliated Hospital, North Sichuan Medical College, Nanchong 737000, China.
authors.forename: Jingguo
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authors.lastname: Zhou
authors.affiliation: The Affiliated Huashan Hospital of Fudan University, Shanghai 20040, China.
authors.forename: Hejian
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authors.lastname: Zou
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 1] Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China [2] Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chen
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Cheng
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Ding
authors.affiliation: 1] Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China [2] Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Tong
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authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: He
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Keke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China [3] Henry Ford Immunology Program, Henry Ford Health System, 1 Ford Place, Detroit, Minnesota 48202, USA.
authors.forename: Congcong
authors.initials: C
authors.lastname: Yin
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Shichao
authors.initials: S
authors.lastname: Xing
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Baojie
authors.initials: B
authors.lastname: Li
authors.affiliation: 1] Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China [2] Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Ji
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Zhaotong
authors.initials: Z
authors.lastname: Jia
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Lidan
authors.initials: L
authors.lastname: Ma
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Jiapeng
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authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xin
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Tian
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authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Chu
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Xuefeng
authors.initials: X
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authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Aiqing
authors.initials: A
authors.lastname: Zhang
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Sun
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Haili
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authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
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authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology of the Affiliated Hospital, North Sichuan Medical College, Nanchong 737000, China.
authors.forename: Yufeng
authors.initials: Y
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authors.affiliation: Department of Endocrinology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, P.R. China.
authors.forename: Gang
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authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Yangang
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authors.affiliation: 1] Henry Ford Immunology Program, Henry Ford Health System, 1 Ford Place, Detroit, Minnesota 48202, USA [2] Department of Dermatology, Henry Ford Health System, 1 Ford Place, Detroit, Michigan 48202, USA [3] Department of Internal Medicine, Henry Ford Health System, 1 Ford Place, Detroit, Michigan 48202, USA.
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authors.affiliation: Department of Urology, The Affiliated Hospital of Medical College Qingdao University, Qingdao 266003, China.
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authors.affiliation: Department of Oncology, The Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, China.
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authors.affiliation: Department of Pediatric Surgery, The Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, P.R. China.
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authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Xinde
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authors.affiliation: 1] Henry Ford Immunology Program, Henry Ford Health System, 1 Ford Place, Detroit, Minnesota 48202, USA [2] Department of Dermatology, Henry Ford Health System, 1 Ford Place, Detroit, Michigan 48202, USA [3] Department of Internal Medicine, Henry Ford Health System, 1 Ford Place, Detroit, Michigan 48202, USA.
authors.forename: Qing-Sheng
authors.initials: QS
authors.lastname: Mi
authors.affiliation: 1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China [3] Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China [4] Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Yongyong
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mesh_terms: D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006073:Gout / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide