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Genetic factors affect the susceptibility to bacterial infections in diabetes

Simonsen, Johan R ; Käräjämäki, Annemari ; Antikainen, Anni A ; Toppila, Iiro ; Ahlqvist, Emma LU ; Prasad, Rashmi LU ; Mansour-Aly, Dina LU ; Harjutsalo, Valma ; Järvinen, Asko and Tuomi, Tiinamaija LU orcid , et al. (2021) In Scientific Reports 11.
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ANDIS, diabetes
in
Scientific Reports
volume
11
article number
9464
publisher
Nature Publishing Group
external identifiers
  • pmid:33947878
  • scopus:85105409266
ISSN
2045-2322
DOI
10.1038/s41598-021-88273-w
language
English
LU publication?
yes
id
76561af8-2934-46a7-a408-6ebdd3096cc3
date added to LUP
2021-10-13 15:55:18
date last changed
2024-06-15 18:10:16
@article{76561af8-2934-46a7-a408-6ebdd3096cc3,
  abstract     = {{<p>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 &lt; 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.</p>}},
  author       = {{Simonsen, Johan R and Käräjämäki, Annemari and Antikainen, Anni A and Toppila, Iiro and Ahlqvist, Emma and Prasad, Rashmi and Mansour-Aly, Dina and Harjutsalo, Valma and Järvinen, Asko and Tuomi, Tiinamaija and Groop, Leif and Forsblom, Carol and Groop, Per-Henrik and Sandholm, Niina and Lehto, Markku}},
  issn         = {{2045-2322}},
  keywords     = {{ANDIS; diabetes}},
  language     = {{eng}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Genetic factors affect the susceptibility to bacterial infections in diabetes}},
  url          = {{http://dx.doi.org/10.1038/s41598-021-88273-w}},
  doi          = {{10.1038/s41598-021-88273-w}},
  volume       = {{11}},
  year         = {{2021}},
}