Genetic factors affect the susceptibility to bacterial infections in diabetes

Johan R Simonsen, Annemari Käräjämäki, Anni A Antikainen, Iiro Toppila, Emma Ahlqvist, Rashmi Prasad, Dina Mansour-Aly, Valma Harjutsalo, Asko Järvinen, Tiinamaija Tuomi, Leif Groop, Carol Forsblom, Per-Henrik Groop, Niina Sandholm, Markku Lehto

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number9464
JournalScientific Reports
Volume11
DOIs
Publication statusPublished - 2021

Subject classification (UKÄ)

  • Endocrinology and Diabetes
  • Infectious Medicine

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