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Browsing by Subject "IBD"

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  • Nihtilä, Julia (2021)
    Henoch-Schölein purpura (HSP) is a vasculitis of small vessels and its characteristics include abnormal accumulation of IgA immunocomplexes on vessel walls as well as abnormal glycosylation patterns of IgA. HSP is an autoimmune disease like inflammatory bowel diseases (IBD). The genetic background of HSP has not been studied in Finnish population before, and only one genome-wide association study has been conducted for HSP before. Therefore investigating the Finnish genetic associations of HSP on a genome-wide level is of value. In this study the genetic background of HSP is studied with genome-wide association analyses performed on 424,041 genotyped SNPs passing quality control, HLA alleles imputed from the SNPs, and for their allele-level HLA protein sequences with the aim of replicating previous HSP associations in a Finnish cohort. There were 46 HSP individuals and 18,757 controls (216 bone marrow donors and 18,541 blood donors) passing quality control and included in the study. R package HIBAG was used for HLA imputation, and SPAtest package was used for the association analyses. In the association analyses, a region in chromosome 6 passed genome-wide significance (SNP with the smallest p-value: p 6,57 x 10-10, OR 0.14[0.1-0.2]) and the region contained both predisposing and protective associations. Of HLA alleles, DQB1*05:01, DQA1*01:01 ja DRB1*01:01 surpassed genome-wide significance level (p values 4,99 x 10-9, 1,04 x 10-8 and 2,37 x 10-8, respectively) and were positively associated with HSP. Five amino acid positions were significantly associated with HSP (p-values 3,9 x 10-10, 7,37 x 10-9, 1,26 x 10-8, 1,69 x 10-8 and 2,41 x 10-8), being both protective and predisposing to HSP. In addition, the genetic background of HSP was compared with that of IBD by comparing their GWAS results of genotyped SNPs, HLA alleles and their protein sequences. There were 49 IBD patients after quality control, and the same controls as for HSP (18,541 individuals) were included in the association analyses of IBD. The diseases seem to share some of their genetic background. According to the results, HSP seems to associate primarily with HLA class 2 and the result is also compatible with previous studies linking HSP to this region. The results also replicate previous GWAS findings in HLA class 2. According to this it is likely that the same HLA alleles are notable genetic factors in both Finnish and Spanish populations. The connection between HSP and IBD could potentially have to do with intestinal microbes aiding the onset of autoimmune diseases in genetically susceptible hosts.