%0 Journal Article %J J Clin Endocrinol Metab %D 2018 %T Trans-ethnic Evaluation Identifies Novel Low Frequency Loci Associated with 25-Hydroxyvitamin D Concentrations. %A Hong, Jaeyoung %A Hatchell, Kathryn E %A Bradfield, Jonathan P %A Andrew, Bjonnes %A Alessandra, Chesi %A Chao-Qiang, Lai %A Langefeld, Carl D %A Lu, Lingyi %A Lu, Yingchang %A Lutsey, Pamela L %A Musani, Solomon K %A Nalls, Mike A %A Robinson-Cohen, Cassianne %A Roizen, Jeffery D %A Saxena, Richa %A Tucker, Katherine L %A Ziegler, Julie T %A Arking, Dan E %A Bis, Joshua C %A Boerwinkle, Eric %A Bottinger, Erwin P %A Bowden, Donald W %A Gilsanz, Vincente %A Houston, Denise K %A Kalkwarf, Heidi J %A Kelly, Andrea %A Lappe, Joan M %A Liu, Yongmei %A Michos, Erin D %A Oberfield, Sharon E %A Palmer, Nicholette D %A Rotter, Jerome I %A Sapkota, Bishwa %A Shepherd, John A %A Wilson, James G %A Basu, Saonli %A de Boer, Ian H %A Divers, Jasmin %A Freedman, Barry I %A Grant, Struan F A %A Hakanarson, Hakon %A Harris, Tamara B %A Kestenbaum, Bryan R %A Kritchevsky, Stephen B %A Loos, Ruth J F %A Norris, Jill M %A Norwood, Arnita F %A Ordovas, Jose M %A Pankow, James S %A Psaty, Bruce M %A Sanhgera, Dharambir K %A Wagenknecht, Lynne E %A Zemel, Babette S %A Meigs, James %A Dupuis, Josée %A Florez, Jose C %A Wang, Thomas %A Liu, Ching-Ti %A Engelman, Corinne D %A Billings, Liana K %X

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.

%B J Clin Endocrinol Metab %8 2018 Jan 09 %G eng %R 10.1210/jc.2017-01802