Serum 25-Hydroxyvitamin D Levels and Youth-Onset Type 2 Diabetes: A Two-Sample Mendelian Randomization Study.

Content Provider	Europe PMC
Author	De La Barrera, Benjamin Manousaki, Despoina
Editor	Barker, Tyler
Copyright Year	2023
Abstract	Observational studies have linked vitamin D insufficiency to pediatric type 2 diabetes (T2D), but evidence from vitamin D supplementation trials is sparse. Given the rising prevalence of pediatric T2D in all ethnicities, determining the protective role of vitamin D has significant public health importance. We tested whether serum 25-hydroxyvitamin D (25OHD) levels are causally linked to youth-onset T2D risk using Mendelian randomization (MR). We selected 54 single-nucleotide polymorphisms (SNPs) associated with 25OHD in a European genome-wide association study (GWAS) on 443,734 individuals and obtained their effects on pediatric T2D from the multi-ethnic PRODIGY GWAS (3006 cases/6061 controls). We applied inverse variance weighted (IVW) MR and a series of MR methods to control for pleiotropy. We undertook sensitivity analyses in ethnic sub-cohorts of PRODIGY, using SNPs in core vitamin D genes or ancestry-informed 25OHD SNPs. Multivariable MR accounted for the mediating effects of body mass index. We found that a standard deviation increase in 25OHD in the logarithmic scale did not affect youth-onset T2D risk (IVW MR odds ratio (OR) = 1.04, 95% CI = 0.96–1.13, p = 0.35) in the multi-ethnic analysis, and sensitivity, ancestry-specific and multivariable MR analyses showed consistent results. Our study had limited power to detect small/moderate effects of 25OHD (OR of pediatric T2D < 1.39 to 2.1). In conclusion, 25OHD levels are unlikely to have significant effects on the risk of youth-onset T2D across different ethnicities.
Journal	Nutrients
Volume Number	15
PubMed Central reference number	PMC9963923
Issue Number	4
PubMed reference number	36839376
e-ISSN	20726643
DOI	10.3390/nu15041016
Language	English
Publisher	MDPI
Publisher Date	2023-02-17
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors.
Subject Keyword	vitamin D pediatric type 2 diabetes Mendelian randomization GWAS causal inference
Content Type	Text
Resource Type	Article
Subject	Food Science Nutrition and Dietetics