Genetic factors affect the susceptibility to bacterial infections in diabetes

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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2106d8063ebe43deac5e9443b38cd8d4
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spelling	oai:doaj.org-article:2106d8063ebe43deac5e9443b38cd8d42021-12-02T14:49:34ZGenetic factors affect the susceptibility to bacterial infections in diabetes10.1038/s41598-021-88273-w2045-2322https://doaj.org/article/2106d8063ebe43deac5e9443b38cd8d42021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88273-whttps://doaj.org/toc/2045-2322Abstract 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.Johan R. SimonsenAnnemari KäräjämäkiAnni A. AntikainenIiro ToppilaEmma AhlqvistRashmi PrasadDina Mansour-AlyValma HarjutsaloAsko JärvinenTiinamaija TuomiLeif GroopCarol ForsblomPer-Henrik GroopNiina SandholmMarkku LehtoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Genetic factors affect the susceptibility to bacterial infections in diabetes
description	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.
format	article
author	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
author_facet	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
author_sort	Johan R. Simonsen
title	Genetic factors affect the susceptibility to bacterial infections in diabetes
title_short	Genetic factors affect the susceptibility to bacterial infections in diabetes
title_full	Genetic factors affect the susceptibility to bacterial infections in diabetes
title_fullStr	Genetic factors affect the susceptibility to bacterial infections in diabetes
title_full_unstemmed	Genetic factors affect the susceptibility to bacterial infections in diabetes
title_sort	genetic factors affect the susceptibility to bacterial infections in diabetes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2106d8063ebe43deac5e9443b38cd8d4
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Genetic factors affect the susceptibility to bacterial infections in diabetes

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