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

TitleTrans-ethnic Evaluation Identifies Novel Low Frequency Loci Associated with 25-Hydroxyvitamin D Concentrations.
Publication TypeJournal Article
Year of Publication2018
AuthorsHong, 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, C-T, Engelman, CD, Billings, LK
JournalJ Clin Endocrinol Metab
Date Published2018 Jan 09
Abstract<p><b>Context: </b>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.</p><p><b>Objective: </b>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.</p><p><b>Design: </b>Ancestry-specific (Hispanic and African) and trans-ethnic (Hispanic, African and European) meta-analyses were performed using the METAL software.</p><p><b>Patients or Other Participants: </b>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.</p><p><b>Main Outcome Measure(s): </b>Blood concentrations of 25(OH)D were measured for all participants.</p><p><b>Results: </b>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.</p><p><b>Conclusions: </b>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.</p>
Alternate JournalJ. Clin. Endocrinol. Metab.
PubMed ID29325163
Grant ListU01 HG007417 / HG / NHGRI NIH HHS / United States
T15 LM007359 / LM / NLM NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
U01 DK078616 / DK / NIDDK NIH HHS / United States
P2C HD047873 / HD / NICHD NIH HHS / United States
U54 GM115428 / GM / NIGMS NIH HHS / United States
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