Genome-wide association study of 25(OH) Vitamin D concentrations in Punjabi Sikhs: Results of the Asian Indian diabetic heart study

J Steroid Biochem Mol Biol. 2016 Apr:158:149-156. doi: 10.1016/j.jsbmb.2015.12.014. Epub 2015 Dec 15.


Vitamin D deficiency is implicated in multiple disease conditions and accumulating evidence supports that the variation in serum vitamin D (25(OH)D) levels, including deficiency, is under strong genetic control. However, the underlying genetic mechanism associated with vitamin 25(OH)D concentrations 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 first genome-wide association study (GWAS) of serum 25(OH)D on 3538 individuals from this Punjabi Sikh population. Our discovery GWAS comprised of 1387 subjects followed by validation of 24 putative SNPs (P<10(-4)) using an independent replication sample (n=2151) from the same population by direct genotyping. A novel locus at chromosome 20p11.21 represented by rs2207173 with minor allele frequency (MAF) 0.29, [β=-0.13, p=4.47×10(-9)] between FOXA2 and SSTR4 was identified to be associated with 25(OH)D levels. Another suggestive association signal at rs11586313 (MAF 0.54) [β=0.90; p=1.36×10(-6)] was found within the regulatory region of the IVL gene on chromosome 1q21.3. Additionally, our study replicated 3 of 5 known GWAS genes associated with 25(OH)D concentrations 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 25(OH)D metabolism will provide new molecular insights on genetic drivers of vitamin D status and its implications in health disparities.

Keywords: 25(OH)D levels (ELISA); Genome-wide association study; Punjabi Sikhs; Type 2 diabetes; Vitamin D deficiency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Variation
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Hydroxycholecalciferols / blood*
  • India / epidemiology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • White People / genetics*


  • Hydroxycholecalciferols