Genetic determinants of Vitamin D deficiency in the Middle Eastern Qatari population: a genome-wide association study

INTRODUCTION: Epidemiological studies have consistently revealed that Vitamin D deficiency is most prevalent in Middle Eastern countries. However, research on the impact of genetic loci and polygenic models related to Vitamin D has primarily focused on European populations. METHODS: We conducted the first genome-wide association study to identify genetic determinants of Vitamin D levels in Middle Easterners using a whole genome sequencing approach in 6,047 subjects from the Qatar Biobank (QBB) project. We performed a GWAS meta-analysis, combining the QBB cohort with recent European GWAS data from the UK Biobank (involving 345,923 individuals). Additionally, we evaluated the performance of European-derived polygenic risk scores using UK Biobank data in the QBB cohort. RESULTS: Our study identified an association between a variant in a known locus for the group-specific component gene (GC), specifically rs2298850 (p-value = 1.71 × 10(−08), Beta = −0.1285), and Vitamin D levels. Furthermore, our GWAS meta-analysis identified two novel variants at a known locus on chromosome 11, rs67609747 and rs1945603, that reached the GWAS significance threshold. Notably, we observed a moderately high heritability of Vitamin D, estimated at 18%, compared to Europeans. Despite the lower predictive performance of Vitamin D levels in Qataris compared to Europeans, the European-derived polygenic risk scores exhibited significant links to Vitamin D deficiency risk within the QBB cohort. CONCLUSION: This novel study reveals the genetic architecture contributing to Vitamin D deficiency in the Qatari population, emphasizing the genetic heterogeneity across different populations.