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

TitleTransethnic Evaluation Identifies Low-Frequency Loci Associated With 25-Hydroxyvitamin D Concentrations.
Publication TypeJournal Article
Year of Publication2018
AuthorsHong J, Hatchell KE, Bradfield JP, Bjonnes A, Chesi A, Lai C-Q, 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 C-T, Engelman CD
Secondary AuthorsBillings LK
JournalJ Clin Endocrinol Metab
Volume103
Issue4
Pagination1380-1392
Date Published2018 04 01
ISSN1945-7197
KeywordsAdolescent, 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
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.

DOI10.1210/jc.2017-01802
Alternate JournalJ Clin Endocrinol Metab
PubMed ID29325163
PubMed Central IDPMC6276579
Grant ListR01 HL103706 / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
R01 DK082766 / DK / NIDDK NIH HHS / United States
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