Vitamin D levels and risk of type 1 diabetes: A Mendelian randomization study

Vitamin D deficiency has been associated with type 1 diabetes in observational studies, but evidence from randomized controlled trials (RCTs) is lacking. The aim of this study was to test whether genetically decreased vitamin D levels are causally associated with type 1 diabetes using Mendelian rand...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	PLoS medicine Ročník 18; číslo 2; s. e1003536
Hlavní autoři:	Manousaki, Despoina, Harroud, Adil, Mitchell, Ruth E., Ross, Stephanie, Forgetta, Vince, Timpson, Nicholas J., Smith, George Davey, Polychronakos, Constantin, Richards, J Brent
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 25.02.2021 Public Library of Science (PLoS)
Témata:	Biology and Life Sciences Biomarkers Causality Clinical trials Complications and side effects Diabetes Diabetes mellitus (insulin dependent) Diabetes Mellitus, Type 1 - complications Diabetes Mellitus, Type 1 - etiology Diabetes Mellitus, Type 1 - genetics Diabetes Mellitus, Type 2 - complications Epidemiology Genetic aspects Genetic diversity Genetic variance Genome-wide association studies Genome-Wide Association Study Genomes Health care Humans Hypotheses Immune system Medicine and Health Sciences Mendelian Randomization Analysis - methods Phenotype Physical sciences Polymorphism, Single Nucleotide - genetics Research and Analysis Methods Risk Factors Single-nucleotide polymorphism Type 1 diabetes Ultraviolet radiation Vitamin D Vitamin D - blood Vitamin D deficiency Vitamin D Deficiency - blood Vitamin D Deficiency - genetics Vitamin deficiency Canada
ISSN:	1549-1676, 1549-1277, 1549-1676
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	Vitamin D deficiency has been associated with type 1 diabetes in observational studies, but evidence from randomized controlled trials (RCTs) is lacking. The aim of this study was to test whether genetically decreased vitamin D levels are causally associated with type 1 diabetes using Mendelian randomization (MR). For our two-sample MR study, we selected as instruments single nucleotide polymorphisms (SNPs) that are strongly associated with 25-hydroxyvitamin D (25OHD) levels in a large vitamin D genome-wide association study (GWAS) on 443,734 Europeans and obtained their corresponding effect estimates on type 1 diabetes risk from a large meta-analysis of 12 type 1 diabetes GWAS studies (Ntot = 24,063, 9,358 cases, and 15,705 controls). In addition to the main analysis using inverse variance weighted MR, we applied 3 additional methods to control for pleiotropy (MR-Egger, weighted median, and mode-based estimate) and compared the respective MR estimates. We also undertook sensitivity analyses excluding SNPs with potential pleiotropic effects. We identified 69 lead independent common SNPs to be genome-wide significant for 25OHD, explaining 3.1% of the variance in 25OHD levels. MR analyses suggested that a 1 standard deviation (SD) decrease in standardized natural log-transformed 25OHD (corresponding to a 29-nmol/l change in 25OHD levels in vitamin D-insufficient individuals) was not associated with an increase in type 1 diabetes risk (inverse-variance weighted (IVW) MR odds ratio (OR) = 1.09, 95% CI: 0.86 to 1.40, p = 0.48). We obtained similar results using the 3 pleiotropy robust MR methods and in sensitivity analyses excluding SNPs associated with serum lipid levels, body composition, blood traits, and type 2 diabetes. Our findings indicate that decreased vitamin D levels did not have a substantial impact on risk of type 1 diabetes in the populations studied. Study limitations include an inability to exclude the existence of smaller associations and a lack of evidence from non-European populations. Our findings suggest that 25OHD levels are unlikely to have a large effect on risk of type 1 diabetes, but larger MR studies or RCTs are needed to investigate small effects.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 I have read the journal’s policy and the authors of this manuscript have the following competing interests:JBR has worked as a consultant to GlaxoSmithKline and Deerfield Capital.GDS is a member of the Editorial Board of PLOS Medicine.
ISSN:	1549-1676 1549-1277 1549-1676
DOI:	10.1371/journal.pmed.1003536