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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #355227
Title: Transethnic evaluation identifies low-frequency loci associated with 25-hydroxyvitamin D concentrations

Author
item HONG, JAEYOUNG - Boston University
item HATCHELL, KATHRYN - University Of Wisconsin
item BRADFIELD, JONATHAN - The Children'S Hospital Of Philadelphia
item BJONNES, ANDREW - Massachusetts General Hospital
item CHESI, ALESSANDRA - The Children'S Hospital Of Philadelphia
item Lai, Chao Qiang
item LANGEFELD, CARL - Wake Forest University
item LU, LINGYI - Wake Forest University
item LU, YINGCHANG - The Icahn School Of Medicine At Mount Sinai
item LUTSEY, PAMELA - University Of Minnesota
item MUSANI, SOLMOMON - University Of Mississippi
item NALLS, MIKE - Data Tecnica International
item ROBINSON-COHEN, CASSIANNE - Vanderbilt University
item ROIZEN, JEFFERY - The Children'S Hospital Of Philadelphia
item SAXENA, RICHA - Massachusetts General Hospital
item TUCKER, KATHERINE - University Of Massachusetts
item ZIEGLER, JULIE - Wake Forest University
item ARKING, DAN - Johns Hopkins University
item BIS, JOSHUA - University Of Washington
item BOERWINKLE, ERIC - University Of Texas
item BOTTINGER, ERWIN - The Icahn School Of Medicine At Mount Sinai
item BOWDEN, DONALD - Wake Forest University
item GILSANZ, VINCENTE - University Of Southern California
item HOUSTON, DENISE - Wake Forest University
item KALKWARF, HEIDI - Children'S Hospital - Cincinnati, Ohio
item KELLY, ANDREA - The Children'S Hospital Of Philadelphia
item LAPPE, JOAN - Creighton University
item LIU, YONGMEI - Wake Forest University
item MICHOS, ERIN - Johns Hopkins University
item OBERFIELD, SHARON - Columbia University
item PALMER, NICHOLETTE - Wake Forest University
item ROTTER, JEROME - Harbor-Ucla Medical Center
item SAPKOTA, BISHWA - University Of Oklahoma
item SHEPHERD, JOHN - University Of California
item WILSON, JAMES - University Of Mississippi
item BASU, SAONLI - University Of Minnesota
item DE BOER, IAN - University Of Washington
item DIVERS, JASMIN - Wake Forest University
item FREEDMAN, BARRY - Wake Forest University
item GRANT, STRUAN - The Children'S Hospital Of Philadelphia
item HAKANARSON, HAKON - The Children'S Hospital Of Philadelphia
item HARRIS, TAMARA - National Institute On Aging (NIA, NIH)
item KESTENBAUM, BRYAN - University Of Washington
item KRITCHEVSKY, STEPHEN - Wake Forest University
item LOOS, RUTH - The Icahn School Of Medicine At Mount Sinai
item NORRIS, JILL - University Of Colorado
item NORWOOD, ARNITA - University Of Mississippi Medical Center
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item PANKOW, JAMES - University Of Minnesota
item PSATY, BRUCE - University Of Washington
item SANGHERA, DHARAMBIR - University Of Oklahoma
item WAGENKNECHT, LYNNE - Wake Forest University
item ZEMEL, BABETTE - The Children'S Hospital Of Philadelphia
item MEIGS, JAMES - Harvard University
item DUPIUS, JOSEE - Boston University
item FLOREZ, JOSE - Broad Institute Of Mit/harvard
item WANG, THOMAS - Vanderbilt University
item LIU, CHING-TI - Boston University
item ENGELMAN, CORINNE - University Of Wisconsin
item BILLINGS, LIANA - Northshore University Health System

Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/3/2018
Publication Date: 1/9/2018
Citation: Hong, J., Hatchell, K.E., Bradfield, J.P., Bjonnes, A., Chesi, A., Lai, C., Langefeld, C.D., Lu, L., Lu, Y., Lutsey, P.L., Musani, S.K., Nalls, M.A., Robinson-Cohen, C., Roizen, J.D., Saxena, R., Tucker, K.L., Ziegler, J.T., Arking, D.E., Bis, J.C., Boerwinkle, E., Bottinger, E.P., Bowden, D.W., Gilsanz, V., Houston, D.K., Kalkwarf, H.J., Kelly, A., Lappe, J.M., Liu, Y., Michos, E.D., Oberfield, S.E., Palmer, N.D., Rotter, J.I., Sapkota, B., Shepherd, J.A., Wilson, J.G., Basu, S., De Boer, I.H., Divers, J., Freedman, B.I., Grant, S.F., Hakanarson, H., Harris, T.B., Kestenbaum, B.R., Kritchevsky, S.B., Loos, R.J., Norris, J.M., Norwood, A.F., Ordovas, J.M., Pankow, J.S., Psaty, B.M., Sanghera, D.K., Wagenknecht, L.E., Zemel, B.S., Meigs, J., Dupius, J., Florez, J.C., Wang, T.J., Liu, C., Engelman, C.D., Billings, L.K. 2018. Transethnic evaluation identifies low-frequency loci associated with 25-hydroxyvitamin D concentrations. Journal of Clinical Endocrinology and Metabolism. 103(4):1380-1392. https://doi.org/10.1210/jc.2017-01802.
DOI: https://doi.org/10.1210/jc.2017-01802

Interpretive Summary: 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. These populations are particularly vulnerable to vitamin D inadequacy because skin-pigmentation affects the vitamin D conversion due to sunlight exposure. This study was designed to identify genetic variants that affect vitamin D concentrations in 8,541 African American, 3,485 Hispanic American and 16,124 European individuals. Genetic variants were identified in the GC and DHCR7 genes that were shared by both Africans and Hispanic Americans and one variant near the KIF4B gene that was specific to African Americans. These findings indicate that the genetic basis of vitamin D inadequacies is population specific.

Technical 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.