Novel identified associations of RGS1 and RASGRP1 variants in IgA Nephropathy.
Known susceptibility loci together can only explain about 6-8% of the disease heritability of IgA nephropathy (IgAN), suggesting that there are still a large number of genetic variants remained to be discovered. We previously identified IgAN and systemic lupus erythematosus (SLE)/lupus nephritis (LN) shared many loci based on GWAS on Chinese populations. The more recent study with high-density genotyping of immune-related loci in individuals with Asian ancestry identified 10 new and 6 suggestive loci in SLE. In the current study, we thus included all the lead SNPs from these 16 loci reported, and firstly tested their associations in 1,248 patients with sporadic IgAN, 737 patients with LN and 1,187 controls. Significant associations identified in IgAN were replicated in additional 500 patients and 2372 controls. rs12022418 in RGS1 (p = 3.0 × 10-6) and rs7170151 in RASGRP1 (p = 1.9 × 10-5) showed novel associations in IgAN. Compared to SNPs that were in LD with them, the associated variants showed higher potential of regulatory features by affecting gene expression. And systemic evaluation of GWAS data supported the pleiotropic effects of RGS1 and RASGRP1 variants in mediating human complex diseases. In conclusion, novel risk loci shared between IgAN and SLE/LN were identified, which may shed new light to exploit the potential pathogenesis for those two diseases.
Renal Division, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; and Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education; Beijing, 100034, People's Republic of China.
Xu-Jie
XJ
Zhou
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Swapan K
SK
Nath
Renal Division, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; and Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education; Beijing, 100034, People's Republic of China.
Yuan-Yuan
YY
Qi
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Celi
C
Sun
Renal Division, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; and Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education; Beijing, 100034, People's Republic of China.
Ping
P
Hou
Renal Division, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; and Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education; Beijing, 100034, People's Republic of China.
Yue-Miao
YM
Zhang
Renal Division, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; and Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education; Beijing, 100034, People's Republic of China.
Ji-Cheng
JC
Lv
Renal Division, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; and Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education; Beijing, 100034, People's Republic of China.
Su-Fang
SF
Shi
Renal Division, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; and Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education; Beijing, 100034, People's Republic of China.
Li-Jun
LJ
Liu
Department of Paediatrics and Adolescent Medicine Centre for Genomic Sciences, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
Ruoyan
R
Chen
Department of Paediatrics and Adolescent Medicine Centre for Genomic Sciences, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
Wanling
W
Yang
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, USA.
Kevin Zhi
KZ
He
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, USA.
Yanming
Y
Li
Renal Division, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; and Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education; Beijing, 100034, People's Republic of China.
Hong
H
Zhang
D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000473:pathology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020710:RGS Proteins / Q000235:genetics*
D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; C491790:RASGRP1 protein, human; D020710:RGS Proteins; C080831:RGS1 protein, human