Trans-ethnic Evaluation Identifies Novel Low Frequency Loci Associated with 25-Hydroxyvitamin D Concentrations.

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Trans-ethnic Evaluation Identifies Novel Low Frequency Loci Associated with 25-Hydroxyvitamin D Concentrations.

J Clin Endocrinol Metab. 2018 Jan 09;:

Authors: Hong J, Hatchell KE, Bradfield JP, Andrew B, Alessandra C, Chao-Qiang L, 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, Sanhgera DK, Wagenknecht LE, Zemel BS, Meigs J, Dupuis J, Florez JC, Wang T, Liu CT, Engelman CD, Billings LK

Abstract
Context: Vitamin D inadequacy is common in the adult population of the United States. While the genetic determinants underlying vitamin D inadequacy have been studied in people of European ancestry, less is known in Hispanic or African ancestry populations.
Objective: The TRANSCEN-D (TRANS-ethniC Evaluation of vitamiN D GWAS) consortium was assembled to replicate genetic associations with 25-hydroxyvitamin D (25(OH)D) concentrations from the meta-analyses of European ancestry (SUNLIGHT) and to identify novel genetic variants related to vitamin D concentrations in African and Hispanic ancestries.
Design: Ancestry-specific (Hispanic and African) and trans-ethnic (Hispanic, African and European) meta-analyses were performed using the METAL software.
Patients or Other Participants: In total, 8,541 African-American and 3,485 Hispanic-American (from North America) participants from twelve cohorts, and 16,124 European participants from SUNLIGHT were included in the study.
Main Outcome Measure(s): Blood concentrations of 25(OH)D were measured for all participants.
Results: Ancestry-specific analyses in African and Hispanic Americans replicated SNPs in GC (2 and 4 SNPs, respectively). A potentially novel SNP (rs79666294) near the KIF4B gene was identified in the African-American cohort. Trans-ethnic evaluation replicated GC and DHCR7 region SNPs. Additionally, the trans-ethnic analyses revealed novel SNPs rs719700 and rs1410656 near the ANO6/ARID2 and HTR2A genes, respectively.
Conclusions: Ancestry-specific and trans-ethnic GWAS of 25(OH)D confirmed findings in GC and DHCR7 for African and Hispanic American samples and revealed novel findings near KIF4B, ANO6/ARID2, and HTR2A. The biological mechanisms that link these regions with 25(OH)D metabolism require further investigation.

PMID: 29325163 [PubMed - as supplied by publisher]

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