Back to Search
Start Over
Low vitamin D and risk of bacterial pneumonias: Mendelian randomisation studies in two population-based cohorts.
- Source :
-
Thorax [Thorax] 2021 May; Vol. 76 (5), pp. 468-478. Date of Electronic Publication: 2020 Oct 27. - Publication Year :
- 2021
-
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.<br />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.<br />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.<br />Conclusions: Low vitamin D is associated observationally and genetically with increased risk of bacterial pneumonias.<br />Competing Interests: Competing interests: YÇ reports personal fees from Boehringer Ingelheim, AstraZeneca, Sanofi Genzyme outside the submitted work. BGN and SA have nothing to disclose.<br /> (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Cholestanetriol 26-Monooxygenase
Cytochrome P450 Family 2
Denmark
Genotype
Humans
Mendelian Randomization Analysis
Middle Aged
Polymorphism, Single Nucleotide
Prospective Studies
Risk
Genetic Predisposition to Disease
Pneumonia, Bacterial genetics
Vitamin D Deficiency genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1468-3296
- Volume :
- 76
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Thorax
- Publication Type :
- Academic Journal
- Accession number :
- 33109689
- Full Text :
- https://doi.org/10.1136/thoraxjnl-2020-215288