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Low vitamin D and risk of bacterial pneumonias: Mendelian randomisation studies in two population-based cohorts.
Thorax. 2020 Oct 27 [Online ahead of print]T

Abstract

BACKGROUND

Vitamin D may regulate the innate immune system, and randomised controlled trials suggest a beneficial effect of vitamin D supplementation against acute respiratory tract infections. By using a Mendelian randomisation approach, we tested the hypothesis that low 25-hydroxyvitamin D is associated with increased risk of bacterial pneumonia in observational and genetic analyses.

METHODS

We genotyped 116 335 randomly chosen white Danes aged 20 to 100 from the Copenhagen City Heart Study and Copenhagen General Population Study for plasma 25-hydroxyvitamin D decreasing genetic variants around CYP2R1 (rs117913124, rs12794714 and rs10741657), DHCR7 (rs7944926 and rs11234027), GEMIN2 (rs2277458) and HAL (rs3819817). Information on plasma 25-hydroxyvitamin D was available on 35 833 individuals. Individuals were followed from 1981 through 2018 for hospital diagnoses of bacterial pneumonias.

RESULTS

During up to 38 years follow-up, we observed 6342 bacterial pneumonias in observational analyses and 13 916 in genetic analyses. In observational analyses, multivariable adjusted HR for bacterial pneumonias was 1.27 (95% CI: 1.16 to 1.40) for individuals with 25-hydroxyvitamin D<25 nmol/L compared with those with ≥25 nmol/L. In genetic analyses, the OR for bacterial pneumonia per 10 nmol/L lower plasma 25-hydroxyvitamin D was 1.12 (95% CI: 1.02 to 1.23) in Wald's ratio, 1.12 (95% CI: 1.04 to 1.20) in inverse-variance weighted, 1.63 (95% CI: 0.96 to 2.78) in MR-Egger and 1.15 (95% CI: 1.05 to 1.26) in weighted median instrumental variable analysis. This association was strongest for genetic variants around CYP2R1. There was no observational or genetic evidence to support that 25-hydroxyvitamin D is associated with risk of urinary tract infections, skin infections, sepsis or gastroenteritis, which were used as negative control outcomes.

CONCLUSIONS

Low vitamin D is associated observationally and genetically with increased risk of bacterial pneumonias.

Authors+Show Affiliations

Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark.Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark shoaib.afzal@regionh.dk. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33109689

Citation

Çolak, Yunus, et al. "Low Vitamin D and Risk of Bacterial Pneumonias: Mendelian Randomisation Studies in Two Population-based Cohorts." Thorax, 2020.
Çolak Y, Nordestgaard BG, Afzal S. Low vitamin D and risk of bacterial pneumonias: Mendelian randomisation studies in two population-based cohorts. Thorax. 2020.
Çolak, Y., Nordestgaard, B. G., & Afzal, S. (2020). Low vitamin D and risk of bacterial pneumonias: Mendelian randomisation studies in two population-based cohorts. Thorax. https://doi.org/10.1136/thoraxjnl-2020-215288
Çolak Y, Nordestgaard BG, Afzal S. Low Vitamin D and Risk of Bacterial Pneumonias: Mendelian Randomisation Studies in Two Population-based Cohorts. Thorax. 2020 Oct 27; PubMed PMID: 33109689.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low vitamin D and risk of bacterial pneumonias: Mendelian randomisation studies in two population-based cohorts. AU - Çolak,Yunus, AU - Nordestgaard,Børge G, AU - Afzal,Shoaib, Y1 - 2020/10/27/ PY - 2020/05/13/received PY - 2020/09/10/revised PY - 2020/10/08/accepted PY - 2020/10/28/entrez PY - 2020/10/29/pubmed PY - 2020/10/29/medline KW - bacterial infection KW - clinical epidemiology KW - innate immunity KW - pneumonia KW - respiratory infection JF - Thorax JO - Thorax N2 - BACKGROUND: Vitamin D may regulate the innate immune system, and randomised controlled trials suggest a beneficial effect of vitamin D supplementation against acute respiratory tract infections. By using a Mendelian randomisation approach, we tested the hypothesis that low 25-hydroxyvitamin D is associated with increased risk of bacterial pneumonia in observational and genetic analyses. METHODS: We genotyped 116 335 randomly chosen white Danes aged 20 to 100 from the Copenhagen City Heart Study and Copenhagen General Population Study for plasma 25-hydroxyvitamin D decreasing genetic variants around CYP2R1 (rs117913124, rs12794714 and rs10741657), DHCR7 (rs7944926 and rs11234027), GEMIN2 (rs2277458) and HAL (rs3819817). Information on plasma 25-hydroxyvitamin D was available on 35 833 individuals. Individuals were followed from 1981 through 2018 for hospital diagnoses of bacterial pneumonias. RESULTS: During up to 38 years follow-up, we observed 6342 bacterial pneumonias in observational analyses and 13 916 in genetic analyses. In observational analyses, multivariable adjusted HR for bacterial pneumonias was 1.27 (95% CI: 1.16 to 1.40) for individuals with 25-hydroxyvitamin D<25 nmol/L compared with those with ≥25 nmol/L. In genetic analyses, the OR for bacterial pneumonia per 10 nmol/L lower plasma 25-hydroxyvitamin D was 1.12 (95% CI: 1.02 to 1.23) in Wald's ratio, 1.12 (95% CI: 1.04 to 1.20) in inverse-variance weighted, 1.63 (95% CI: 0.96 to 2.78) in MR-Egger and 1.15 (95% CI: 1.05 to 1.26) in weighted median instrumental variable analysis. This association was strongest for genetic variants around CYP2R1. There was no observational or genetic evidence to support that 25-hydroxyvitamin D is associated with risk of urinary tract infections, skin infections, sepsis or gastroenteritis, which were used as negative control outcomes. CONCLUSIONS: Low vitamin D is associated observationally and genetically with increased risk of bacterial pneumonias. SN - 1468-3296 UR - https://www.unboundmedicine.com/medline/citation/33109689/Low_vitamin_D_and_risk_of_bacterial_pneumonias:_Mendelian_randomisation_studies_in_two_population-based_cohorts L2 - https://thorax.bmj.com/lookup/pmidlookup?view=long&amp;pmid=33109689 DB - PRIME DP - Unbound Medicine ER -
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