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Genetic Determinants of Antibody-Mediated Immune Responses to Infectious Diseases Agents: A Genome-Wide and HLA Association Study.

ABSTRACT: Background:Infectious diseases are causally related to a large array of noncommunicable diseases (NCDs). Identifying genetic determinants of infections and antibody-mediated immune responses may shed light on this relationship and provide therapeutic targets for drug and vaccine development. Methods:We used the UK biobank cohort of up to 10 000 serological measurements of infectious diseases and genome-wide genotyping. We used data on 13 pathogens to define 46 phenotypes: 15 seropositivity case-control phenotypes and 31 quantitative antibody measurement phenotypes. For each of these, we performed genome-wide association studies (GWAS) using the fastGWA linear mixed model package and human leukocyte antigen (HLA) classical allele and amino acid residue associations analyses using Lasso regression for variable selection. Results:We included a total of 8735 individuals for case-control phenotypes, and an average (range) of 4286 (276-8555) samples per quantitative analysis. Fourteen of the GWAS yielded a genome-wide significant (P?

SUBMITTER: Butler-Laporte G

PROVIDER: S-EPMC7641500 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Genetic Determinants of Antibody-Mediated Immune Responses to Infectious Diseases Agents: A Genome-Wide and HLA Association Study.

Butler-Laporte Guillaume G Kreuzer Devin D Nakanishi Tomoko T Harroud Adil A Forgetta Vincenzo V Richards J Brent JB

Open forum infectious diseases 20200924 11

<h4>Background</h4>Infectious diseases are causally related to a large array of noncommunicable diseases (NCDs). Identifying genetic determinants of infections and antibody-mediated immune responses may shed light on this relationship and provide therapeutic targets for drug and vaccine development.<h4>Methods</h4>We used the UK biobank cohort of up to 10 000 serological measurements of infectious diseases and genome-wide genotyping. We used data on 13 pathogens to define 46 phenotypes: 15 serop ...[more]

PMID: 33204752

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Project description:BackgroundRecent studies increasingly suggest that microbial infections and the immune responses they elicit play significant roles in the pathogenesis of chronic inflammatory skin diseases. This study uses Mendelian randomization (MR) and Bayesian weighted Mendelian randomization (BWMR) to explore the causal relationships between immune antibody responses and four common skin diseases: psoriasis, atopic dermatitis (AD), rosacea, and vitiligo.MethodsWe utilized summary statistics from genome-wide association studies (GWAS) for antibody responses to 13 infectious pathogens and four skin diseases. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) to assess causal relationships using multiple MR methods, including inverse variance weighted (IVW), MR Egger, and weighted median. BWMR was also employed to confirm findings and address potential pleiotropy.ResultsThe IVW analysis identified significant associations between specific antibody responses and the skin diseases studied. Key findings include protective associations of anti-Epstein-Barr virus (EBV) IgG seropositivity and Helicobacter pylori UREA antibody levels with psoriasis and AD. anti-chlamydia trachomatis IgG seropositivity, anti-polyomavirus 2 IgG seropositivity, and varicella zoster virus glycoprotein E and I antibody levels were negatively associated with rosacea, while EBV Elevated levels of the early antigen (EA-D) antibody levels and HHV-6 IE1B antibody levels were positively associated with rosacea. H. pylori Catalase antibody levels were protectively associated with vitiligo, whereas anti-herpes simplex virus 2 (HSV-2) IgG seropositivity was positively associated with vitiligo. The BWMR analysis confirmed these associations.ConclusionThis study underscores the significant role of H. pylori and other pathogens in these skin diseases, suggesting both protective and exacerbating effects depending on the specific condition. Understanding these pathogen-immune interactions can lead to the development of more effective, personalized treatments and preventative strategies, ultimately improving patient outcomes and quality of life.

Dataset Information

Genetic Determinants of Antibody-Mediated Immune Responses to Infectious Diseases Agents: A Genome-Wide and HLA Association Study.

Publications

Genetic Determinants of Antibody-Mediated Immune Responses to Infectious Diseases Agents: A Genome-Wide and HLA Association Study.

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