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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\u2009=\u20095092, Diabetes Registry Vaasa; N\u2009=\u20094247) using national register data on antibiotic prescription purchases. Replication analyses were performed in a Swedish diabetic population (ANDIS; N\u2009=\u20099602) and in a Finnish non-diabetic population (FinnGen; N\u2009=\u2009159,166). Genome-wide data indicated moderate but significant narrow-sense heritability for infection susceptibility (h<jats:sup>2<\/jats:sup>\u2009=\u200916%, P\u2009=\u20090.02). Variants on chromosome 2 were associated with reduced infection susceptibility (rs62192851, P\u2009=\u20092.23\u2009\u00d7\u200910<jats:sup>\u20137<\/jats:sup>). Homozygotic carriers of the rs62192851 effect allele (N\u2009=\u200944) had a 37% lower median annual antibiotic purchase rate, compared to homozygotic carriers of the reference allele (N\u2009=\u20094231): 0.38 [IQR 0.22\u20130.90] and 0.60 [0.30\u20131.20] respectively, P\u2009=\u20090.01). Variants rs6727834 and rs10188087, in linkage disequilibrium with rs62192851, replicated in the FinnGen-cohort (P\u2009&lt;\u20090.05), but no variants replicated in the ANDIS-cohort. Pathway analysis suggested the <jats:italic>IRAK1<\/jats:italic> mediated NF-\u03baB 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.<\/jats:p>","DOI":"10.1038\/s41598-021-88273-w","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T10:03:29Z","timestamp":1620122609000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genetic factors affect the susceptibility to bacterial infections in diabetes"],"prefix":"10.1038","volume":"11","author":[{"given":"Johan R.","family":"Simonsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemari","family":"K\u00e4r\u00e4j\u00e4m\u00e4ki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anni A.","family":"Antikainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iiro","family":"Toppila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Ahlqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Prasad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Mansour-Aly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valma","family":"Harjutsalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asko","family":"J\u00e4rvinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiinamaija","family":"Tuomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif","family":"Groop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Forsblom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per-Henrik","family":"Groop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niina","family":"Sandholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markku","family":"Lehto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,4]]},"reference":[{"key":"88273_CR1","doi-asserted-by":"publisher","first-page":"e1002355","DOI":"10.1371\/journal.pgen.1002355","volume":"7","author":"M Fumagalli","year":"2011","unstructured":"Fumagalli, M. et al. 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He has received lecture fees from Astellas, Astra Zeneca, Boehringer-Ingelheim, Eli Lilly, Genzyme, M.S.D., Novartis, Novo Nordisk, Peer Voice, Sanofi and SCIARC. Asko J\u00e4rvinen has received lecture fees from Astellas, Biogen, MSD, OrionPharma, Pfizer and UnimedicPharma and consultation fee from CSL Behring and UnimedicPharma. Iiro Toppila is currently employed by Medaffcon Oy, Espoo, Finland. All other authors declare that there is no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"9464"}}