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dc.contributor.authorFlatby, Helene Marie
dc.contributor.authorRasheed, Humaira
dc.contributor.authorRavi, Anuradha
dc.contributor.authorThomas, Laurent
dc.contributor.authorLiyanarachi, Kristin Vardheim
dc.contributor.authorAfset, Jan Egil
dc.contributor.authorDeWan, Andrew
dc.contributor.authorBrumpton, Ben Michael
dc.contributor.authorHveem, Kristian
dc.contributor.authorÅsvold, Bjørn Olav
dc.contributor.authorSimonsen, Gunnar Skov
dc.contributor.authorFurberg, Anne-Sofie
dc.contributor.authorDamås, Jan Kristian
dc.contributor.authorSolligård, Erik
dc.contributor.authorRogne, Tormod
dc.date.accessioned2022-03-03T10:11:01Z
dc.date.available2022-03-03T10:11:01Z
dc.date.issued2021-11-09
dc.description.abstractObjective: Lower respiratory tract infections (LRTIs) are a leading cause of morbidity and mortality worldwide. Few studies have previously investigated the genetic susceptibility and potential risk factors for LRTI. Methods: We used data from UK Biobank, HUNT, and FinnGen, to conduct a genome-wide association study (GWAS). Cases were subjects hospitalized with LRTI, and controls were subjects with no such hospitalization. We conducted stratification and interaction analyses to evaluate if the genetic effect of LRTI differed by sex or smoking. Mendelian randomization [MR] analyses were conducted to identify the unconfounded relationship between cardiometabolic risk factors and LRTI. Results: A total of 25,320 cases and 575,294 controls were included. The 15q25.1 locus reached genome-wide significance in the meta-analysis (rs10519203: OR = 0.94, P = 3.87e-11). The protective effect of effect allele of rs10519203 was present among smokers (OR = 0.90 [95% CI = 0.87 - 0.92, P = 1.38e-15]) but not among never-smokers (OR = 1.01 [95% CI = 0.97 - 1.06, P = 5.20e-01]). In MR analyses, we found that increasing body mass index (OR = 1.31 [95% CI = 1.24 - 1.40, P = 3.78e-18]), lifetime smoking (OR = 2.83 [95% CI = 2.34 - 3.42, P = 6.56e-27]), and systolic blood pressure robustly increased the risk of LRTIs (OR = 1.11 [95% CI = 1.02 - 1.22, P = 1.48e-02]). Conclusion: A region in 15q25.1 was strongly associated with LRTI susceptibility. Reduction of the prevalence of smoking, overweight, obesity, and hypertension may reduce the disease burden of LRTIs.en_US
dc.identifier.citationFlatby HM, Rasheed H, Ravi A, Thomas LF, Liyanarachi KV, Afset JE, DeWan A, Brumpton BM, Hveem K, Åsvold BO, Simonsen GS, Furberg A-S, Damås JK, Solligård E, Rogne T. Risk of lower respiratory tract infections: a genome-wide association study with Mendelian randomization analysis in three independent European populations. Clinical Microbiology and Infection (CMI). 2021en_US
dc.identifier.cristinIDFRIDAID 1953002
dc.identifier.doi10.1016/j.cmi.2021.11.004
dc.identifier.issn1198-743X
dc.identifier.issn1469-0691
dc.identifier.urihttps://hdl.handle.net/10037/24240
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalClinical Microbiology and Infection (CMI)
dc.relation.urihttps://doi.org/10.1016/j.cmi.2021.11.004
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.titleRisk of lower respiratory tract infections: a genome-wide association study with Mendelian randomization analysis in three independent European populationsen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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