Identification of new susceptibility loci for IgA nephropathy in Han Chinese

被引：99

作者：

Li, Ming ^{[1
,2
]}

Foo, Jia-Nee ^{[3
]}

Wang, Jin-Quan ^{[4
]}

Low, Hui-Qi ^{[3
]}

Tang, Xue-Qing ^{[1
,2
]}

Toh, Kai-Yee ^{[3
]}

Yin, Pei-Ran ^{[1
,2
]}

Khor, Chiea-Chuen ^{[3
,5
,6
,7
]}

Goh, Yu-Fen ^{[3
]}

Irwan, Ishak D. ^{[3
]}

Xu, Ri-Cong ^{[1
,2
]}

Andiappan, Anand K. ^{[8
]}

Bei, Jin-Xin ^{[3
]}

Rotzschke, Olaf ^{[8
]}

Chen, Meng-Hua ^{[9
]}

Cheng, Ching-Yu ^{[5
,6
,7
]}

Sun, Liang-Dan ^{[10
,11
,12
]}

Jiang, Geng-Ru ^{[13
]}

Wong, Tien-Yin ^{[5
,6
,7
]}

Lin, Hong-Li ^{[14
]}

Aung, Tin ^{[5
,6
,7
]}

Liao, Yun-Hua ^{[15
]}

Saw, Seang-Mei ^{[5
,7
,16
]}

Ye, Kun ^{[17
]}

Ebstein, Richard P. ^{[18
]}

Chen, Qin-Kai ^{[19
]}

Shi, Wei ^{[20
]}

Chew, Soo-Hong ^{[21
]}

Chen, Jian ^{[22
]}

Zhang, Fu-Ren ^{[23
]}

Li, Sheng-Ping ^{[24
]}

Xu, Gang ^{[25
]}

Tai, E. Shyong ^{[26
,27
]}

Wang, Li ^{[28
]}

Chen, Nan ^{[29
]}

Zhang, Xue-Jun ^{[10
,11
,12
]}

Zeng, Yi-Xin ^{[30
,31
]}

Zhang, Hong ^{[32
]}

Liu, Zhi-Hong ^{[4
]}

Yu, Xue-Qing ^{[1
]}

Liu, Jian-Jun ^{[1
,3
,10
,11
,16
,33
,34
]}

机构：

[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Nephrol, Guangzhou 510080, Guangdong, Peoples R China

[2] Minist Hlth & Guangdong Prov, Key Lab Nephrol, Guangzhou 510080, Guangdong, Peoples R China

[3] Agcy Sci Technol & Res, Genome Inst Singapore, Human Genet, Singapore 138672, Singapore

[4] Nanjing Univ, Sch Med, Jinling Hosp, Natl Clin Res Ctr Kidney Dis, Nanjing 210002, Jiangsu, Peoples R China

[5] Singapore Eye Res Inst, Singapore 169856, Singapore

[6] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 119228, Singapore

[7] Natl Univ Hlth Syst, Singapore 119228, Singapore

[8] Agcy Sci Technol & Res, Singapore Immunol Network, Singapore 138648, Singapore

[9] Ningxia Med Univ, Gen Hosp, Dept Nephrol, Ningxia 750004, Peoples R China

[10] Anhui Med Univ, Inst Dermatol, Hefei 230032, Anhui, Peoples R China

[11] Anhui Med Univ, Hosp 1, Dept Dermatol, Hefei 230032, Anhui, Peoples R China

[12] Minist Natl Sci & Technol, State Key Lab Incubat Base Dermatol, Hefei 230032, Anhui, Peoples R China

[13] Shanghai Jiao Tong Univ, Sch Med, XinHua Hosp, Dept Nephrol, Shanghai 200092, Peoples R China

[14] Dalian Med Univ, Affiliated Hosp 1, Dept Nephrol, Dalian 116011, Liaoning, Peoples R China

[15] Guangxi Med Univ, Affiliated Hosp 1, Dept Nephrol, Nanning 530021, Peoples R China

[16] Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117549, Singapore

[17] Peoples Hosp Guangxi Autonomous Reg, Dept Nephrol, Nanning, Guangxi, Peoples R China

[18] Natl Univ Singapore, Dept Psychol, Singapore 117570, Singapore

[19] Nanchang Univ, Affiliated Hosp 1, Dept Nephrol, Nanchang 330006, Jiangxi, Peoples R China

[20] Guangdong Gen Hosp, Dept Nephrol, Guangzhou 510080, Guangdong, Peoples R China

[21] Natl Univ Singapore, Dept Econ, Singapore 117570, Singapore

[22] Fuzhou Gen Hosp Nanjing Mil Command, Dept Nephrol, Fuzhou 350025, Fujian, Peoples R China

[23] Shandong Acad Med Sci, Shandong Prov Inst Dermatol & Venereol, Jinan 250000, Shandong, Peoples R China

[24] Sun Yat Sen Univ, Ctr Canc, Dept Hepatobiliary Oncol, State Key Lab Oncol South China, Guangzhou 510080, Guangdong, Peoples R China

[25] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Nephrol, Wuhan 430030, Hunan, Peoples R China

[26] Duke Natl Univ Singapore, Grad Sch Med, Singapore 169857, Singapore

[27] Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 119228, Singapore

[28] Sichuan Prov Peoples Hosp, Dept Nephrol, Chengdu 610072, Sichuan, Peoples R China

[29] Shanghai Jiao Tong Univ, Sch Med, RuiJin Hosp, Dept Nephrol, Shanghai 200025, Peoples R China

[30] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510080, Guangdong, Peoples R China

[31] Chinese Acad Med Sci, Peking Union Med Coll, Beijing 100730, Peoples R China

[32] Peking Univ, Inst Nephrol, Hosp 1, Div Renal, Beijing 100034, Peoples R China

[33] Anhui Med Univ, Sch Biol Sci, Hefei 230032, Anhui, Peoples R China

[34] Anhui Med Univ, Hosp 1, Inst Dermatol, Hefei 230032, Anhui, Peoples R China

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

高等学校博士学科点专项科研基金; 中国国家自然科学基金;

关键词：

GENOME-WIDE ASSOCIATION; GENE COPY NUMBER; OXFORD CLASSIFICATION; GENOTYPE IMPUTATION; ALPHA-DEFENSIN; STRATIFICATION; RESOURCE; COMPLEX; LINKAGE; EXT1;

D O I：

10.1038/ncomms8270

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 x 10(-10)), ACCS on 11p11.2 (rs2074038, OR = 1.14, P = 3.93 x 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR = 1.13, P = 1.41 x 10(-9)), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR = 1.22, P = 2.26 x 10(-19)), and identify three independent signals within the DEFA locus (rs2738058, P = 1.15 x 10(-19); rs12716641, P = 9.53 x 10(-9); s9314614, P = 4.25 x 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.

引用

页数：9

共 50 条

[21] Association analyses identify three new susceptibility loci for vitiligo in the Chinese Han population
Sun Liang-dan
Tang Xian-fa
Zhang Zheng
Hu Da-yan
Xu Ai-e
Zhou Hai-sheng
Yang Sen
Zhang Xue-jun
JOURNAL OF DERMATOLOGY, 2012, 39 : 225 - 225
[22] Identification of susceptibility loci for cognitive impairment in a cohort of Han Chinese patients with Parkinson's disease
Liu, Hong-Jun
Li, Xiao-Yan
Chen, Hui
Yu, Hui-Li
Tao, Qing-Qing
Wu, Zhi-Ying
NEUROSCIENCE LETTERS, 2020, 730
[23] Replication of Migraine GWAS Susceptibility Loci in Chinese Han Population
Fan, Xiaoping
Wang, Jing
Fan, Wen
Chen, Lixue
Gui, Bei
Tan, Ge
Zhou, Jiying
HEADACHE, 2014, 54 (04): : 709 - 715
[24] COMBINED EFFECT OF ESTABLISHED IGA NEPHROPATHY SUSCEPTIBILITY LOCI ON DISEASE PROGRESSION
Shi, Manman
Ouyang, Yan
Yang, Mingxin
Yang, Meng
Zhang, Xiaoyan
Huang, Wei
Wang, Weiming
Wang, Zhaohui
Zhang, Wen
Chen, Xiaonong
Pan, Xiaoxia
Ren, Hong
Chen, Nan
Xie, Jingyuan
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2018, 33 : 82 - 82
[25] 3′ untranslated region variants in DEFA5 gene associated with susceptibility to IgA nephropathy in the Chinese Han population
Peng, Hongwei
Fan, Pingyun
Hong, Yifen
He, Jing
Zeng, Xiangxiu
Xu, Fengguo
Zhao, Yunxia
Jin, Tianbo
BIOMARKERS IN MEDICINE, 2022, 16 (16) : 1151 - 1159
[26] Interaction of C1GALT1-IL5RA on the susceptibility to IgA nephropathy in Southern Han Chinese
Wang, Wei
Sun, Yu
Fu, Yonggui
Yu, Xueqing
Li, Ming
JOURNAL OF HUMAN GENETICS, 2013, 58 (01) : 40 - 46
[27] Exome Chip Analyses and Genetic Risk for IgA Nephropathy among Han Chinese
Zhou, Xu-jie
Tsoi, Lam C.
Hu, Yong
Patrick, Matthew T.
He, Kevin
Berthier, Celine C.
Li, Yanming
Wang, Yan-na
Qi, Yuan-yuan
Zhang, Yue-miao
Gan, Ting
Li, Yang
Hou, Ping
Liu, Li-jun
Shi, Su-fang
Lv, Ji-cheng
Xu, Hu-ji
Zhang, Hong
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2021, 16 (02): : 213 - 224
[28] Association Study Confirmed Susceptibility Loci with Keloid in the Chinese Han Population
Zhu, Fei
Wu, Baoyu
Li, Ping
Wang, Jianbo
Tang, Huayang
Liu, Ye
Zuo, Xianbo
Cheng, Hui
Ding, Yantao
Wang, Wen
Zhai, Yujuan
Qian, Fangfang
Wang, Wenju
Yuan, Xiangfeng
Wang, Jing
Ha, Weiwei
Hou, Junsheng
Zhou, Fusheng
Wang, Yin
Gao, Jinping
Sheng, Yujun
Sun, Liangdan
Liu, Jianjun
Yang, Sen
Zhang, Xuejun
PLOS ONE, 2013, 8 (05):
[29] Association of TNFSF13 polymorphisms with IgA nephropathy in a Chinese Han population
Zhong, Zhong
Feng, Shao-Zhen
Xu, Ri-Cong
Li, Zhi-Jian
Huang, Feng-Xian
Yin, Pei-Ran
Liu, Wen-Ting
Wang, Meng
Shi, Dian-Chun
Zhou, Qian
Yu, Xue-Qing
Li, Ming
JOURNAL OF GENE MEDICINE, 2017, 19 (6-7):
[30] Validation of Susceptibility Loci for Vitiligo Identified by GWAS in the Chinese Han Population
Cheng, Lu
Liang, Bo
Tang, Xian-Fa
Cai, Xin-Ying
Cheng, Hui
Zheng, Xiao-Dong
Zheng, Jie
Wang, Meng-Wei
Zhu, Jun
Zhou, Fu-Sheng
Li, Pan
Xiao, Feng-Li
FRONTIERS IN GENETICS, 2020, 11

← 1 2 3 4 5 →