Transethnic Evaluation Identifies Low-Frequency Loci Associated With 25-Hydroxyvitamin D Concentrations.

Hong J, Hatchell KE, Bradfield JP, Bjonnes A, Chesi A, Lai CQ, Langefeld CD, Lu L, Lu Y, Lutsey PL, Musani SK, Nalls MA, Robinson-Cohen C, Roizen JD, Saxena R, Tucker KL, Ziegler JT, Arking DE, Bis JC, Boerwinkle E, Bottinger EP, Bowden DW, Gilsanz V, Houston DK, Kalkwarf HJ, Kelly A, Lappe JM, Liu Y, Michos ED, Oberfield SE, Palmer ND, Rotter JI, Sapkota B, Shepherd JA, Wilson JG, Basu S, de Boer IH, Divers J, Freedman BI, Grant SFA, Hakanarson H, Harris TB, Kestenbaum BR, Kritchevsky SB, Loos RJF, Norris JM, Norwood AF, Ordovas JM, Pankow JS, Psaty BM, Sanghera DK, Wagenknecht LE, Zemel BS, Meigs J, Dupuis J, Florez JC, Wang T, Liu CT, Engelman CD, Billings LK
J Clin Endocrinol Metab. 2018 103 (4): 1380-1392

PMID: 29325163 · PMCID: PMC6276579 · DOI:10.1210/jc.2017-01802

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.

MeSH Terms (20)

Adolescent Adult African Americans Aged Body Mass Index Child European Continental Ancestry Group Female Gene Frequency Genetic Loci Genome-Wide Association Study Hispanic Americans Humans Male Middle Aged Polymorphism, Single Nucleotide United States Vitamin D Vitamin D Deficiency Young Adult

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