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Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA Nephropathy.

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收录情况： ◇ SCIE

作者：
Ming Li[1,2] ; Ling Wang[3] ; Dian-Chun Shi[1,2,4] ; Jia-Nee Foo[3,5] ; Zhong Zhong[1,2] ; Chiea-Chuen Khor[3,6] ; Chiara Lanzani[7] ; Lorena Citterio[7] ; Erika Salvi[8] ; Pei-Ran Yin[1,2] ; Jin-Xin Bei[9,10] ; Li Wang[11] ; Yun-Hua Liao[12] ; Jian Chen[13] ; Qin-Kai Chen[14] ; Gang Xu[15] ; Geng-Ru Jiang[16] ; Jian-Xin Wan[17] ; Meng-Hua Chen[18] ; Nan Chen[19] ; Hong Zhang[20] ; Yi-Xin Zeng[9,10] ; Zhi-Hong Liu[21] ; Jian-Jun Liu[3,4,22,*2] ; Xue-Qing Yu[1,2,4,23,*1] ;
机构： [1]Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China [2]National Health Commission Key Laboratory of Nephrology (Sun Yat-sen University), Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China [3]Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore [4]Guangdong Provincial People’s Hospital, Guangzhou, China [5]Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore [6]Singapore Eye Research Institute, Singapore, Singapore [7]Genomics of Renal Diseases and Hypertension Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy [8]Neurology Unit, IRCCS Neurology Institute “Carlo Besta,” Milan, Italy [9]Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China [10]State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China [11]Department of Nephrology, Sichuan Provincial People’s Hospital, Chengdu, China [12]Department of Nephrology, The First Affiliated Hospital, Guangxi Medical University, Nanning, China [13]Department of Nephrology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, China [14]Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, China [15]Department of Nephrology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China [16]Department of Nephrology, XinHua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China [17]Department of Nephrology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China [18]Department of Nephrology, General Hospital of Ningxia Medical University, Yinchuan, China [19]Department of Nephrology, RuiJin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China [20]Renal Division, Peking University First Hospital, Peking University, Institute of Nephrology, Beijing, China [21]National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China [22]Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore [23]School of Medicine, South China University of Technology, Guangzhou, China
出处：
DOI： 10.1681/ASN.2019080799
ISSN：

摘要：
Eighteen known susceptibility loci for IgAN account for only a small proportion of IgAN risk. Genome-wide meta-analysis was performed in 2628 patients and 11,563 controls of Chinese ancestry, and a replication analysis was conducted in 6879 patients and 9019 controls of Chinese descent and 1039 patients and 1289 controls of European ancestry. The data were used to assess the association of susceptibility loci with clinical phenotypes for IgAN, and to investigate genetic heterogeneity of IgAN susceptibility between the two populations. Imputation-based analysis of the MHC/HLA region extended the scrutiny. Identification of three novel loci (rs6427389 on 1q23.1 [P=8.18×10-9, OR=1.132], rs6942325 on 6p25.3 [P=1.62×10-11, OR=1.165], and rs2240335 on 1p36.13 [P=5.10×10-9, OR=1.114]), implicates FCRL3, DUSP22.IRF4, and PADI4 as susceptibility genes for IgAN. Rs2240335 is associated with the expression level of PADI4, and rs6427389 is in high linkage disequilibrium with rs11264799, which showed a strong expression quantitative trail loci effect on FCRL3. Of the 24 confirmed risk SNPs, six showed significant heterogeneity of genetic effects and DEFA showed clear evidence of allelic heterogeneity between the populations. Imputation-based analysis of the MHC region revealed significant associations at three HLA polymorphisms (HLA allele DPB1*02, AA_DRB1_140_32657458_T, and AA_DQA1_34_32717152) and two SNPs (rs9275464 and rs2295119). A meta-analysis of GWAS data revealed three novel genetic risk loci for IgAN, and three HLA polymorphisms and two SNPs within the MHC region, and demonstrated the genetic heterogeneity of seven loci out of 24 confirmed risk SNPs.  These variants may explain susceptibility differences between Chinese and European populations. Copyright © 2020 by the American Society of Nephrology.

基金：
This work was funded by the National Key Research and Development Program grant 2016YFC0906100; Guangdong Provincial Key Laboratory operational grant 2017B030314019; Guangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney Diseases grant 2019B121205005; Science and Technology Planning Project of Guangdong Province grants 2017A050503003 and 2017B020227006; National Natural Science Foundation of China grants 81770661, 81570599, and 81920108008; Science and Technology Planning Project of Guangzhou City grant 2016201604030005; National Research Foundation Singapore fellowship grant NRF-NRFF2016-03; and the Agency for Science, Technology and Research (A*STAR) of Singapore (to J. Liu).
语种：
外文
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中科院(CAS)分区：
出版当年[2020]版：
大类 | 1 区 医学
小类 | 1 区 泌尿学与肾脏学
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 泌尿学与肾脏学
JCR分区：
出版当年[2020]版：
Q1 UROLOGY & NEPHROLOGY
最新[2023]版：
Q1 UROLOGY & NEPHROLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China [2]National Health Commission Key Laboratory of Nephrology (Sun Yat-sen University), Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China [2]National Health Commission Key Laboratory of Nephrology (Sun Yat-sen University), Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China [3]Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore [4]Guangdong Provincial People’s Hospital, Guangzhou, China [22]Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore [23]School of Medicine, South China University of Technology, Guangzhou, China [*1]Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University. Key Laboratory of Nephrology, Ministry of Health.Guangdong Provincial People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510080, People’s Republic of China [*2]Department of Human Genetics, Genome Institute of Singapore, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
推荐引用方式(GB/T 7714)：
Ming Li,Ling Wang,Dian-Chun Shi,et al.Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA Nephropathy.[J].JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY.2020,31(12):2949-2963.doi:10.1681/ASN.2019080799.
APA：
Ming Li,Ling Wang,Dian-Chun Shi,Jia-Nee Foo,Zhong Zhong...&Xue-Qing Yu.(2020).Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA Nephropathy..JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY,31,(12)
MLA：
Ming Li,et al."Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA Nephropathy.".JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 31..12(2020):2949-2963

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