Genetic factors affect the susceptibility to bacterial infections in diabetes
(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.
(Less)
- author
- organization
- publishing date
- 2021
- 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 < 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}}, }