1. Transethnic Evaluation Identifies Low-Frequency Loci Associated With 25-Hydroxyvitamin D Concentrations
- Author
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Arnita F. Norwood, Thomas J. Wang, Stephen B. Kritchevsky, Joan M. Lappe, Katherine L. Tucker, James G. Wilson, Carl D. Langefeld, Yingchang Lu, Andrew Bjonnes, Pamela L. Lutsey, Jaeyoung Hong, James S. Pankow, James B. Meigs, Joshua C. Bis, Jose M. Ordovas, Jeffery D. Roizen, Tamara B. Harris, Nicholette D. Palmer, Chao-Qiang Lai, Erwin P. Bottinger, Hakon Hakanarson, Jasmin Divers, Lingyi Lu, Kathryn E. Hatchell, Saonli Basu, Bryan Kestenbaum, Yongmei Liu, Heidi J. Kalkwarf, Cassianne Robinson-Cohen, Bishwa Raj Sapkota, John A. Shepherd, Sharon E. Oberfield, Lynne E. Wagenknecht, Donald W. Bowden, Eric Boerwinkle, Andrea Kelly, Ian H. de Boer, Josée Dupuis, Alessandra Chesi, Bruce M. Psaty, Babette S. Zemel, Vicente Gilsanz, Ching-Ti Liu, Richa Saxena, Struan F.A. Grant, Dan E. Arking, Jonathan P. Bradfield, Corinne D. Engelman, Solomon K. Musani, Denise K. Houston, Barry I. Freedman, Mike A. Nalls, Dharambir K. Sanghera, Julie T. Ziegler, Jill M. Norris, Jerome I. Rotter, Jose C. Florez, Ruth J. F. Loos, Erin D. Michos, and Liana K. Billings
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Context (language use) ,Single-nucleotide polymorphism ,Genome-wide association study ,Biology ,Biochemistry ,Polymorphism, Single Nucleotide ,White People ,Body Mass Index ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Endocrinology ,Gene Frequency ,Polymorphism (computer science) ,Internal medicine ,medicine ,Vitamin D and neurology ,SNP ,Humans ,030212 general & internal medicine ,Vitamin D ,Child ,Allele frequency ,Clinical Research Articles ,Aged ,Genetics ,Biochemistry (medical) ,Hispanic or Latino ,Middle Aged ,Vitamin D Deficiency ,United States ,Black or African American ,030104 developmental biology ,Genetic Loci ,Cohort ,Female ,Genome-Wide Association Study - Abstract
Context Vitamin D inadequacy is common in the adult population of the United States. Although the genetic determinants underlying vitamin D inadequacy have been studied in people of European ancestry, less is known about populations with Hispanic or African ancestry. Objective The Trans-Ethnic Evaluation of Vitamin D (TRANSCEN-D) genomewide association study (GWAS) consortium was assembled to replicate genetic associations with 25-hydroxyvitamin D [25(OH)D] concentrations from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) meta-analyses of European ancestry and to identify genetic variants related to vitamin D concentrations in African and Hispanic ancestries. Design Ancestry-specific (Hispanic and African) and transethnic (Hispanic, African, and European) meta-analyses were performed with Meta-Analysis Helper software (METAL). Patients or Other Participants In total, 8541 African American and 3485 Hispanic American (from North America) participants from 12 cohorts and 16,124 European participants from SUNLIGHT were included in the study. Main Outcome Measures Blood concentrations of 25(OH)D were measured for all participants. Results Ancestry-specific analyses in African and Hispanic Americans replicated single nucleotide polymorphisms (SNPs) in GC (2 and 4 SNPs, respectively). An SNP (rs79666294) near the KIF4B gene was identified in the African American cohort. Transethnic evaluation replicated GC and DHCR7 region SNPs. Additionally, the transethnic analyses revealed SNPs rs719700 and rs1410656 near the ANO6/ARID2 and HTR2A genes, respectively. Conclusions Ancestry-specific and transethnic GWASs of 25(OH)D confirmed findings in GC and DHCR7 for African and Hispanic American samples and revealed findings near KIF4B, ANO6/ARID2, and HTR2A. The biological mechanisms that link these regions with 25(OH)D metabolism warrant further investigation.
- Published
- 2018