Open AccessGenome‐wide association study of 7661 Chinese Han individuals and fine‐mapping major histocompatibility complex identifies HLA‐DRB1 as associated with IgA vasculitis
Author(s) -
Xia Liang,
Chen Mengyun,
Zhang Hanshuo,
Zheng Xiaodong,
Bao Jing,
Gao Jinping,
Zhu Caihong,
Sun Liangdan,
Xia Hailong,
Zhang Xuejun
Publication year - 2022
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.24457
Subject(s) - human leukocyte antigen , genome wide association study , major histocompatibility complex , biology , genetics , allele , immunology , hla drb1 , genetic association , antigen , genotype , single nucleotide polymorphism , gene
Background Immunoglobulin‐A vasculitis (IgAV) is an immune‐related systemic vasculitis with an unclear etiology. Genetic predisposition is now considered to be closely associated with the development of the disease, and it is essential to reveal the relationship between them. To explore the role of heredity in the disease, we performed a genome‐wide association study (GWAS) of 496 IgAV cases and 7165 controls using an Illumina Infinium Global Screening Array chip. Methods In the first stage of analysis, a significant correlation between the major histocompatibility complex (MHC) and IgAV was observed. Subsequently, human leukocyte antigen (HLA) analysis was conducted using a new large‐scale Han‐MHC reference panel. Fine mapping of IgAV risk in the MHC region indicated that two amino acid positions, 120 and 11, of HLA‐DRB1 and three potential HLA alleles (HLA‐DRB1∗04, HLA‐DRB1∗16, and HLA‐DRB1∗16:02) were significantly associated. Results Further stepwise conditional analysis demonstrated that 3 amino acid positions (120, 26, 96) of HLA‐DRB1 and 6 HLA‐DRB1 alleles (HLA‐DRB1*04, HLA‐DRB1*16, HLA‐DRB1*01, HLA‐DRB1*12:02, HLA‐DRB1*10, and HLA‐DRB1*15:02) were independent signals. Among them, the most significant signal was HLA‐DRB1 amino acid Ser120 (OR = 1.59, p = 3.19 × 10 −8 ); no independent signal in the MHC region except for HLA‐DRB1 was found. Conclusions Our study confirms that the pathogenesis of IgAV has a genetic component and that HLA‐DRB1 is strongly associated with susceptibility to IgAV.