Genetic factors affect the susceptibility to bacterial infections in diabetes

Sci Rep. 2021 May 4;11(1):9464. doi: 10.1038/s41598-021-88273-w.

Abstract

Diabetes increases the risk of bacterial infections. We investigated whether common genetic variants associate with infection susceptibility in Finnish diabetic individuals. We performed genome-wide association studies and pathway analysis for bacterial infection frequency in Finnish adult diabetic individuals (FinnDiane Study; N = 5092, Diabetes Registry Vaasa; N = 4247) using national register data on antibiotic prescription purchases. Replication analyses were performed in a Swedish diabetic population (ANDIS; N = 9602) and in a Finnish non-diabetic population (FinnGen; N = 159,166). Genome-wide data indicated moderate but significant narrow-sense heritability for infection susceptibility (h2 = 16%, P = 0.02). Variants on chromosome 2 were associated with reduced infection susceptibility (rs62192851, P = 2.23 × 10-7). Homozygotic carriers of the rs62192851 effect allele (N = 44) had a 37% lower median annual antibiotic purchase rate, compared to homozygotic carriers of the reference allele (N = 4231): 0.38 [IQR 0.22-0.90] and 0.60 [0.30-1.20] respectively, P = 0.01). Variants rs6727834 and rs10188087, in linkage disequilibrium with rs62192851, replicated in the FinnGen-cohort (P < 0.05), but no variants replicated in the ANDIS-cohort. Pathway analysis suggested the IRAK1 mediated NF-κB activation through IKK complex recruitment-pathway to be a mediator of the phenotype. Common genetic variants on chromosome 2 may associate with reduced risk of bacterial infections in Finnish individuals with diabetes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bacterial Infections / genetics*
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / microbiology*
  • Female
  • Finland
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study / methods
  • Genotype
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics*