Dharambir K Sanghera, Bishwa R Sapkota, Ruth Hopkins and Piers R Blackett
University of Oklahoma Health Sciences Center, USA
Posters & Accepted Abstracts: J Diabetes Metab
Vitamin D deficiency is implicated in multiple disease conditions and accumulating evidence supports that the variation in serum vitamin D levels, including deficiency, is under strong genetic control. However, the underlying genetic mechanism associated with circulating vitamin D levels is poorly understood. We earlier reported a very high prevalence of vitamin D deficiency associated with an increased risk for type 2 diabetes and obesity in a Punjabi Sikh diabetic cohort as part of the Asian Indian Diabetic Heart Study (AIDHS). Here we have performed the genome-wide association study (GWAS) of circulating serum vitamin D levels on 3, 538 individuals. Our discovery GWAS comprised of 1, 387 subjects followed by validation of 24 putative SNPs (P<10-4) using an independent replication sample (n=2, 151) from the same population by direct genotyping. One novel locus at chromosome 20p11.21with minor allele frequency (MAF) 0.29, [β = -0.13, p=4.47x10-9] between FOXA2 and SSTR4, and another suggestive locus at chromosome 1q21.3 (MAF 0.54) [β = 0.90; p=1.36x10-6] within the regulatory region of the IVL gene were identified to be associated with circulating serum vitamin D levels. Additionally, we replicated 3 of 5 known GWAS genes influencing serum vitamin D levels including GC (p=0.007) and CYP2R1 (p=0.019) reported in Europeans and the DAB1 (p=0.003), reported in Hispanics. Identification of novel association signals in biologically plausible regions with vitamin D metabolism will provide new molecular insights on genetic drivers of vitamin D status and its implications in health disparities.
Email: Dharambir-Sanghera@ouhsc.edu
