Genome‐wide association study of 7661 Chinese Han individuals and fine‐mapping major histocompatibility complex identifies HLA‐DRB1 as associated with IgA vasculitis. Issue 6 (25th April 2022)

• Record Type: Journal Article
• Authors: Xia, Liang; Chen, Mengyun; Zhang, Hanshuo; Zheng, Xiaodong; Bao, Jing; Gao, Jinping; Zhu, Caihong; Sun, Liangdan; Xia, Hailong; Zhang, Xuejun
• Is Part Of: Journal of clinical laboratory analysis. Volume 36:Issue 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-04-25
• Subjects: Henoch‐Schönlein purpura -- HLA‐DRB1 -- Immunoglobulin‐A vasculitis -- susceptibility; Diagnosis, Laboratory -- Periodicals; Medical laboratory technology -- Periodicals; 616
• DOI: 10.1002/jcla.24457
• Languages: English
• ISSNs: 0887-8013

Abstract

Abstract: 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. Abstract : The summary of genome‐wide association results for 496 cases and 7165 controls. (a) The genome‐wide p values (−log10 p ) of logistic regression analysis adjusted for sex (19, 899 SNPs) plotted against the position on chromosome 6. (b) Quantile–quantile plots of the observed p values versus the expected values from the p value of association. The plot in black is based on the entire set of 377, 302 SNPs.