Genome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
25
09
2020
accepted:
26
04
2021
entrez:
20
5
2021
pubmed:
21
5
2021
medline:
25
2
2023
Statut:
epublish
Résumé
Relative to European Americans, African Americans have lower 25-hydroxyvitamin D (25OHD) and vitamin D binding protein (VDBP) concentrations, higher 1,25-dihydroxyvitamin D (1,25(OH)2D3) concentrations and bone mineral density (BMD), and paradoxically reduced burdens of calcified atherosclerotic plaque (subclinical atherosclerosis). To identify genetic factors contributing to vitamin D and BMD measures, association analysis of >14M variants was conducted in a maximum of 697 African American-Diabetes Heart Study participants with type 2 diabetes (T2D). The most significant association signals were detected for VDBP on chromosome 4; variants rs7041 (β = 0.44, SE = 0.019, P = 9.4x10-86) and rs4588 (β = 0.17, SE = 0.021, P = 3.5x10-08) in the group-specific component (vitamin D binding protein) gene (GC). These variants were found to be independently associated. In addition, rs7041 was also associated with bioavailable vitamin D (BAVD; β = 0.16, SE = 0.02, P = 3.3x10-19). Six rare variants were significantly associated with 25OHD, including a non-synonymous variant in HSPG2 (rs116788687; β = -1.07, SE = 0.17, P = 2.2x10-10) and an intronic variant in TNIK (rs143555701; β = -1.01, SE = 0.18, P = 9.0x10-10), both biologically related to bone development. Variants associated with 25OHD failed to replicate in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Evaluation of vitamin D metabolism and bone mineral density phenotypes in an African American population enriched for T2D could provide insight into ethnic specific differences in vitamin D metabolism and bone mineral density.
Identifiants
pubmed: 34014961
doi: 10.1371/journal.pone.0251423
pii: PONE-D-20-30282
pmc: PMC8136717
doi:
Substances chimiques
Vitamin D-Binding Protein
0
Vitamin D
1406-16-2
1,25-dihydroxyvitamin D
66772-14-3
25-hydroxyvitamin D
A288AR3C9H
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0251423Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR048797
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG058921
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL067348
Pays : United States
Organisme : NIMHD NIH HHS
ID : P20 MD006899
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK071891
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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