title: Genome-wide association study of 25(OH) Vitamin D concentrations in Punjabi Sikhs: Results of the Asian Indian diabetic heart study.
abstract: 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.
authors.affiliation: Department of Pediatrics, Section of Genetics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Bishwa R
authors.initials: BR
authors.lastname: Sapkota
authors.affiliation: Department of Pediatrics, Section of Genetics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Hopkins
authors.affiliation: Broad Institute of Massachusetts Institute of Technology and Harvard, Massachusetts General Hospital, Cambridge, MA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bjonnes
authors.affiliation: Hero DMC Heart Institute, Ludhiana, India.
authors.forename: Sarju
authors.initials: S
authors.lastname: Ralhan
authors.affiliation: Hero DMC Heart Institute, Ludhiana, India.
authors.forename: Gurpreet S
authors.initials: GS
authors.lastname: Wander
authors.affiliation: All India Institute of Medical Sciences and Research, New Delhi, India.
authors.forename: Narinder K
authors.initials: NK
authors.lastname: Mehra
authors.affiliation: Central University of Punjab, Bathinda, Punjab, India.
authors.forename: Jai Rup
authors.initials: JR
authors.lastname: Singh
authors.affiliation: Department of Pediatrics, Section of Endocrinology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Piers R
authors.initials: PR
authors.lastname: Blackett
authors.affiliation: Broad Institute of Massachusetts Institute of Technology and Harvard, Massachusetts General Hospital, Cambridge, MA, USA.
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
authors.affiliation: Department of Pediatrics, Section of Genetics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address: Dharambir-sanghera@ouhsc.edu.
authors.forename: Dharambir K
authors.initials: DK
authors.lastname: Sanghera
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006887:Hydroxycholecalciferols / Q000097:blood*; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
chemical_list: D006887:Hydroxycholecalciferols
keywords: 25(OH)D levels (ELISA); Genome-wide association study; Punjabi Sikhs; Type 2 diabetes; Vitamin D deficiency