Frontiers in nutrition · 2023
Genetic determinants of Vitamin D deficiency in the Middle Eastern Qatari population: a genome-wide association study.
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Hendi Nagham Nafiz, Al-Sarraj Yasser, Ismail Umlai Umm-Kulthum, Suhre Karsten, Nemer Georges, Albagha Omar
Аннотация
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.
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.