title: Identification of new susceptibility loci for IgA nephropathy in Han Chinese.
abstract: IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, odds ratio (OR)=1.13, P=7.27 × 10(-10)), ACCS on 11p11.2 (rs2074038, OR=1.14, P=3.93 × 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR=1.13, P=1.41 × 10(-9)), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR=1.22, P=2.26 × 10(-19)), and identify three independent signals within the DEFA locus (rs2738058, P=1.15 × 10(-19); rs12716641, P=9.53 × 10(-9); rs9314614, P=4.25 × 10(-9), multivariate association). The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants within ST6GAL1, ACCS and DEFA correlate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou , Guangdong 510080, China.|Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, Guangdong 510080, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
authors.forename: Jia-Nee
authors.initials: JN
authors.lastname: Foo
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, China.
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Wang
authors.affiliation: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
authors.forename: Hui-Qi
authors.initials: HQ
authors.lastname: Low
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou , Guangdong 510080, China.|Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, Guangdong 510080, China.
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Tang
authors.affiliation: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
authors.forename: Kai-Yee
authors.initials: KY
authors.lastname: Toh
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou , Guangdong 510080, China.|Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, Guangdong 510080, China.
authors.forename: Pei-Ran
authors.initials: PR
authors.lastname: Yin
authors.affiliation: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.|Singapore Eye Research Institute, Singapore 169856, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore.
authors.forename: Chiea-Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Goh
authors.affiliation: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
authors.forename: Ishak D
authors.initials: ID
authors.lastname: Irwan
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou , Guangdong 510080, China.|Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, Guangdong 510080, China.
authors.forename: Ri-Cong
authors.initials: RC
authors.lastname: Xu
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
authors.forename: Anand K
authors.initials: AK
authors.lastname: Andiappan
authors.affiliation: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
authors.forename: Jin-Xin
authors.initials: JX
authors.lastname: Bei
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
authors.forename: Olaf
authors.initials: O
authors.lastname: Rotzschke
authors.affiliation: Department of Nephrology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Meng-Hua
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Singapore Eye Research Institute, Singapore 169856, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Institute of Dermatology and Department of Dermatology, No.1 Hospital, Anhui Medical University, Hefei, Anhui, 230032, China.|State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Hefei, Anhui 230032, China.
authors.forename: Liang-Dan
authors.initials: LD
authors.lastname: Sun
authors.affiliation: Department of Nephrology, XinHua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Geng-Ru
authors.initials: GR
authors.lastname: Jiang
authors.affiliation: Singapore Eye Research Institute, Singapore 169856, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore.
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, China.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Lin
authors.affiliation: Singapore Eye Research Institute, Singapore 169856, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore.
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors.forename: Yun-Hua
authors.initials: YH
authors.lastname: Liao
authors.affiliation: Singapore Eye Research Institute, Singapore 169856, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore 117549, Singapore.
authors.forename: Seang-Mei
authors.initials: SM
authors.lastname: Saw
authors.affiliation: Department of Nephrology, The People's Hospital of Guangxi Autonomous Region, Nanning, Guangxi 530021, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Ye
authors.affiliation: Department of Psychology, National University of Singapore, Singapore 117570, Singapore.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Ebstein
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Qin-Kai
authors.initials: QK
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Guangdong General Hospital, Guangzhou, Guangdong 510080, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Economics, National University of Singapore, Singapore 117570, Singapore.
authors.forename: Soo-Hong
authors.initials: SH
authors.lastname: Chew
authors.affiliation: Department of Nephrology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian 350025, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Science, Jinan, Shandong 250000, China.
authors.forename: Fu-Ren
authors.initials: FR
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510080, China.
authors.forename: Sheng-Ping
authors.initials: SP
authors.lastname: Li
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College of Huazhong University of science &Technology, Wuhan, Hubei 430030, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Duke-National University of Singapore Graduate Medical School, Singapore 169857, Singapore.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 119228, Singapore.
authors.forename: E
authors.initials: E
authors.lastname: Shyong Tai
authors.affiliation: Department of Nephrology, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Nephrology, RuiJin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
authors.affiliation: Institute of Dermatology and Department of Dermatology, No.1 Hospital, Anhui Medical University, Hefei, Anhui, 230032, China.|State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Hefei, Anhui 230032, China.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510080, China.|Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.affiliation: Renal Division, Peking University First Hospital, Peking University, Institute of Nephrology, Beijing 100034, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Liu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou , Guangdong 510080, China.
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Yu
authors.affiliation: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore 117549, Singapore.|School of Biological Sciences, Anhui Medical University, Hefei, Anhui 230032, China.|Institute of Dermatology and Department of Dermatology, No.1 Hospital, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Liu
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D039481:CD11b Antigen / Q000235:genetics; D039521:CD11c Antigen / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D026281:DEFICIENS Protein / Q000235:genetics; D051765:Early Growth Response Transcription Factors / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008190:Lyases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012799:Sialyltransferases / Q000235:genetics; D055815:Young Adult; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; D039521:CD11c Antigen; D026281:DEFICIENS Protein; D051765:Early Growth Response Transcription Factors; D006360:Heat-Shock Proteins; D051741:Kruppel-Like Transcription Factors; D008190:Lyases; D012799:Sialyltransferases; C509295:ITGAM protein, human; C098111:KLF10 protein, human; C086058:ODF1 protein, human; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase; C021773:1-aminocyclopropanecarboxylate synthase