Global Genetic Variation in Circulating 25-Hydroxyvitamin D: A Systematic Review of GWAS Evidence Across Different Ancestral Groups.
Level 3 - non-randomized controlled study
Systematic review of observational genome-wide association studies (graded by study design analogy).
PubMed 42451056 · doi:10.3390/nu18132052
What was done
The authors conducted a systematic review following PRISMA 2020 guidelines by searching PubMed and the GWAS Catalog for genome-wide association studies (GWAS) investigating genetic variants associated with circulating 25-hydroxyvitamin D (25OHD) concentrations across diverse ancestries. Eligible studies were assessed for methodological quality and statistical power adequacy. Genome-wide significant SNPs were extracted, grouped by ancestry, clustered into genomic windows, and evaluated for linkage disequilibrium (LD) structure.
What was found
Across 15 included GWAS, 349 genome-wide significant SNP associations were identified, representing 294 unique variants (283 indexed in dbSNP). Fifteen variants replicated in at least two independent cohorts. Variant discovery was dominated by European-ancestry populations, though African, East Asian, Hispanic/Latino, Middle Eastern, South Asian, and trans-ethnic cohorts contributed signals. Variant aggregation and strong LD clustering centered on core vitamin D metabolism loci across ancestries, specifically GC, CYP2R1, DHCR7/NADSYN1, and FLG. Potential ancestry-specific variants were observed but remained inconclusive due to low statistical power in non-European groups.
Why it matters
This synthesis demonstrates that circulating vitamin D levels are universally regulated by a core set of metabolic genes across global ancestries, while highlighting a stark disparity in genetic discovery due to the underrepresentation of non-European populations.
Limits
The findings are heavily biased toward European-ancestry cohorts, leaving non-European populations underpowered to reliably confirm or refute ancestry-specific associations. Effect sizes, specific variance explained, and total participant counts across the 15 studies were not reported in the abstract.
Cited by
- supports Single nucleotide polymorphisms affect the enzymatic steps required to convert vitamin D3 into 25-hydroxyvitamin D.