Identification of susceptibility loci and relevant cell type for IgA nephropathy in Han Chinese by integrative genome-wide analysis  

作　　者：Ming Li Xingjie Hao Dianchun Shi Shanshan Cheng Zhong Zhong Lu Cai Minghui Jiang Lin Ding Lanbo Ding Chaolong Wang Xueqing Yu 

机构地区：[1]Department of Nephrology,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,China [2]Department of Nephrology,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China [3]Guangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney Diseases,Guangzhou 510080,China [4]Department of Epidemiology and Biostatistics,Ministry of Education Key Laboratory of Environment and Health,School of Public Health,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [5]NHC Key Laboratory of Nephrology(Sun Yat-sen University),and Guangdong Provincial Key Laboratory of Nephrology,Guangzhou 510080,China

出　　处：《Frontiers of Medicine》2024年第5期862-877,共16页医学前沿（英文版）

基　　金：supported by Guangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney Diseases(No.2019B121205005);National Natural Science Foundation of China(Nos.81920108008,81770661,82170714,and 82003561);Guangzhou Municipal Science and Technology Project of China(No.202201011246);Basic and Applied Basic Research Foundation of Guangdong Province(No.2021A1515111054);Fundamental Research Funds for the Central Universities(No.2019kfyXJJS036).

摘　　要：Although many susceptibility loci for IgA nephropathy(IgAN)have been identified,they only account for 11.0%of the overall IgAN variance.We performed a large genome-wide meta-analysis of IgAN in Han Chinese with 3616 cases and 10417 controls to identify additional genetic loci of IgAN.Considering that inflammatory bowel disease(IBD)and asthma might share an etiology of dysregulated mucosal immunity with IgAN,we performed cross-trait integrative analysis by leveraging functional annotations of relevant cell type and the pleiotropic information from IBD and asthma.Among 8669456 imputed variants,we identified a novel locus at 4p14 containing the long noncoding RNA LOC101060498.Cell type enrichment analysis based on annotations suggested that PMA-I-stimulated CD4+CD25–IL17+Th17 cell was the most relevant cell type for IgAN,which highlights the essential role of Th17 pathway in the pathogenesis of IgAN.Furthermore,we identified six more novel loci associated with IgAN,which included three loci showing pleiotropic effects with IBD or asthma(2q35/PNKD,6q25.2/SCAF8,and 22q11.21/UBE2L3)and three loci specific to IgAN(14q32.32/TRAF3,16q22.2/TXNL4B,and 21q21.3/LINC00113)in the pleiotropic analysis.Our findings support the involvement of mucosal immunity,especially T cell immune response and IL-17 signal pathway,in the development of IgAN and shed light on further investigation of IgAN.

关 键 词：IgA nephropathy(IgAN) genome-wide association study(GWAS) relevant cell types integrative analysis PLEIOTROPY 

分 类 号：R692[医药卫生—泌尿科学]