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- Title
Serum 25-Hydroxyvitamin D Levels and Youth-Onset Type 2 Diabetes: A Two-Sample Mendelian Randomization Study.
- Authors
De La Barrera, Benjamin; Manousaki, Despoina
- 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.
- Subjects
BIOMARKERS; STATISTICAL power analysis; CONFIDENCE intervals; SERUM; SINGLE nucleotide polymorphisms; MULTIVARIATE analysis; CHILDHOOD obesity; GENETIC variation; CASE-control method; VITAMIN D; TYPE 2 diabetes; RISK assessment; GENOME-wide association studies; AGE factors in disease; DESCRIPTIVE statistics; BODY mass index; ODDS ratio; EPIDEMIOLOGICAL research; DISEASE risk factors; ADOLESCENCE
- Publication
Nutrients, 2023, Vol 15, Issue 4, p1016
- ISSN
2072-6643
- Publication type
Article
- DOI
10.3390/nu15041016