A genome-wide association study identifies 25(OH)D3-associated genetic variants in the prediabetic Chinese population

Objectives Diabetes mellitus has been a significant public health problem, associated with high rates of morbidity, disability, and mortality. Prediabetes is a crucial period for preventing and managing diabetes. 25(OH)D3 is an important risk factor for prediabetes. However, there is limited genetic knowledge of 25(OH)D3 in the Chinese population. This study was designed to identify genetic variants associated with 25(OH)D3 and explore the potential pathogenesis of prediabetes. Methods In this study, 451 individuals with prediabetes were recruited to determine the genetic variants associated with 25(OH)D3 through a genome-wide association study (GWAS). Gene mapping and overrepresentation analysis (ORA) were further performed to explore the candidate genes and their biological mechanisms. Results In this study, we identified two independent significant loci (rs9457733 and rs11243373, p < 5 x 10(-6) and r(2) < 0.6) and 37 candidate genes associated with 25(OH)D3 in prediabetes. Furthermore, the ORA analysis revealed that two genes in the gene sets, SLC22A1 and SLC22A3, were found to be significantly enriched in monoamine transmembrane transporter activity and quaternary ammonium group transmembrane transporter activity, as determined by WebGestalt and g:Profiler (p(adj) < 0.05). Conclusion The identification of potential genes associated with 25(OH)D3 provides a foundation for a better understanding of the pathogenesis, diagnosis, and treatment of prediabetes.