A genome-wide association study in a large community-based cohort identifies multiple loci associated with susceptibility to bacterial and viral infections

• Published in: Scientific reports Vol. 12; no. 1; pp. 2582 - 14
• Main Authors: Tängdén, Thomas, Gustafsson, Stefan, Rao, Abhiram S., Ingelsson, Erik
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-02-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/205/2138; 692/699/255; Abdomen; Adult; Aged; Bacteria; Bacteria - isolation & purification; Bacterial Infections - epidemiology; Bacterial Infections - genetics; Bacterial Infections - immunology; Bacterial Infections - pathology; Biobanks; Biological Specimen Banks - statistics & numerical data; Case-Control Studies; Cohort Studies; Cytokines; Diabetes mellitus; DQA1 protein; Drb1 protein; Drug development; Female; Gene expression; Gene mapping; Genes, MHC Class I; Genes, MHC Class II; Genetic diversity; Genetic Predisposition to Disease; Genetic variance; Genome-wide association studies; Genome-Wide Association Study; Genomes; Histocompatibility antigen HLA; Humanities and Social Sciences; Humans; Immune system; Immunosuppressive agents; Infections; Infectious diseases; Leukocytes; Male; Middle Aged; multidisciplinary; Patients; Phenotypes; Polymorphism, Single Nucleotide; Population studies; Quantitative Trait Loci; Rheumatoid arthritis; Science; Science (multidisciplinary); Sepsis; Single-nucleotide polymorphism; United Kingdom - epidemiology; Viral infections; Virus Diseases - epidemiology; Virus Diseases - genetics; Virus Diseases - immunology; Virus Diseases - pathology; Viruses - isolation & purification; United Kingdom; United Kingdom > UK
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-05838-z

There is limited data on host-specific genetic determinants of susceptibility to bacterial and viral infections. Genome-wide association studies using large population cohorts can be a first step towards identifying patients prone to infectious diseases and targets for new therapies. Genetic variants associated with clinically relevant entities of bacterial and viral infections (e.g., abdominal infections, respiratory infections, and sepsis) in 337,484 participants of the UK Biobank cohort were explored by genome-wide association analyses. Cases (n = 81,179) were identified based on ICD-10 diagnosis codes of hospital inpatient and death registries. Functional annotation was performed using gene expression (eQTL) data. Fifty-seven unique genome-wide significant loci were found, many of which are novel in the context of infectious diseases. Some of the detected genetic variants were previously reported associated with infectious, inflammatory, autoimmune, and malignant diseases or key components of the immune system (e.g., white blood cells, cytokines). Fine mapping of the HLA region revealed significant associations with HLA-DQA1, HLA-DRB1, and HLA-DRB4 locus alleles.
PPP1R14A
showed strong colocalization with abdominal infections and gene expression in sigmoid and transverse colon, suggesting causality. Shared significant loci across infections and non-infectious phenotypes in the UK Biobank cohort were found, suggesting associations for example between SNPs identified for abdominal infections and CRP, rheumatoid arthritis, and diabetes mellitus. We report multiple loci associated with bacterial and viral infections. A better understanding of the genetic determinants of bacterial and viral infections can be useful to identify patients at risk and in the development of new drugs.