John Jeffrey Carr
Professor of Radiology, Biomedical Informatics and Cardiovascular Medicine
Last active: 1/10/2020

Admixture mapping of serum vitamin D and parathyroid hormone concentrations in the African American-Diabetes Heart Study.

Palmer ND, Divers J, Lu L, Register TC, Carr JJ, Hicks PJ, Smith SC, Xu J, Judd SE, Irvin MR, Gutierrez OM, Bowden DW, Wagenknecht LE, Langefeld CD, Freedman BI
Bone. 2016 87: 71-7

PMID: 27032714 · PMCID: PMC4862915 · DOI:10.1016/j.bone.2016.01.028

Vitamin D and intact parathyroid hormone (iPTH) concentrations differ between individuals of African and European descent and may play a role in observed racial differences in bone mineral density (BMD). These findings suggest that mapping by admixture linkage disequilibrium (MALD) may be informative for identifying genetic variants contributing to these ethnic disparities. Admixture mapping was performed for serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, vitamin D-binding protein (VDBP), bioavailable vitamin D, and iPTH concentrations and computed tomography measured thoracic and lumbar vertebral volumetric BMD in 552 unrelated African Americans with type 2 diabetes from the African American-Diabetes Heart Study. Genotyping was performed using a custom Illumina ancestry informative marker (AIM) panel. For each AIM, the probability of inheriting 0, 1, or 2 copies of a European-derived allele was determined. Non-parametric linkage analysis was performed by testing for association between each AIM using these probabilities among phenotypes, accounting for global ancestry, age, and gender. Fine-mapping of MALD peaks was facilitated by genome-wide association study (GWAS) data. VDBP levels were significantly linked in proximity to the protein coding locus (rs7689609, LOD=11.05). Two loci exhibited significant linkage signals for 1,25-dihydroxyvitamin D on 13q21.2 (rs1622710, LOD=3.20) and 12q13.2 (rs11171526, LOD=3.10). iPTH was significantly linked on 9q31.3 (rs7854368, LOD=3.14). Fine-mapping with GWAS data revealed significant known (rs7041 with VDBP, P=1.38×10(-82)) and novel (rs12741813 and rs10863774 with VDBP, P<6.43×10(-5)) loci with plausible biological roles. Admixture mapping in combination with fine-mapping has focused efforts to identify loci contributing to ethnic differences in vitamin D-related traits.

Copyright © 2016 Elsevier Inc. All rights reserved.

MeSH Terms (12)

African Americans Demography Diabetes Mellitus, Type 2 Female Humans Linkage Disequilibrium Lod Score Male Middle Aged Parathyroid Hormone Polymorphism, Single Nucleotide Vitamin D

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