Genome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study.
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 pla...
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2021
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oai:doaj.org-article:1db08e71b48b43f89880d407c287f3602021-11-25T06:23:46ZGenome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study.1932-620310.1371/journal.pone.0251423https://doaj.org/article/1db08e71b48b43f89880d407c287f3602021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251423https://doaj.org/toc/1932-6203Relative 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.Nicholette D PalmerLingyi LuThomas C RegisterLeon LenchikJ Jeffrey CarrPamela J HicksS Carrie SmithJianzhao XuLatchezar DimitrovJacob KeatonMeijian GuanMaggie C Y NgYii-der I ChenAnthony J HanleyCorinne D EngelmanJill M NorrisCarl D LangefeldLynne E WagenknechtDonald W BowdenBarry I FreedmanJasmin DiversPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251423 (2021) |
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| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Nicholette D Palmer Lingyi Lu Thomas C Register Leon Lenchik J Jeffrey Carr Pamela J Hicks S Carrie Smith Jianzhao Xu Latchezar Dimitrov Jacob Keaton Meijian Guan Maggie C Y Ng Yii-der I Chen Anthony J Hanley Corinne D Engelman Jill M Norris Carl D Langefeld Lynne E Wagenknecht Donald W Bowden Barry I Freedman Jasmin Divers Genome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study. |
| description |
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. |
| format |
article |
| author |
Nicholette D Palmer Lingyi Lu Thomas C Register Leon Lenchik J Jeffrey Carr Pamela J Hicks S Carrie Smith Jianzhao Xu Latchezar Dimitrov Jacob Keaton Meijian Guan Maggie C Y Ng Yii-der I Chen Anthony J Hanley Corinne D Engelman Jill M Norris Carl D Langefeld Lynne E Wagenknecht Donald W Bowden Barry I Freedman Jasmin Divers |
| author_facet |
Nicholette D Palmer Lingyi Lu Thomas C Register Leon Lenchik J Jeffrey Carr Pamela J Hicks S Carrie Smith Jianzhao Xu Latchezar Dimitrov Jacob Keaton Meijian Guan Maggie C Y Ng Yii-der I Chen Anthony J Hanley Corinne D Engelman Jill M Norris Carl D Langefeld Lynne E Wagenknecht Donald W Bowden Barry I Freedman Jasmin Divers |
| author_sort |
Nicholette D Palmer |
| title |
Genome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study. |
| title_short |
Genome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study. |
| title_full |
Genome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study. |
| title_fullStr |
Genome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study. |
| title_full_unstemmed |
Genome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study. |
| title_sort |
genome-wide association study of vitamin d concentrations and bone mineral density in the african american-diabetes heart study. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/1db08e71b48b43f89880d407c287f360 |
| work_keys_str_mv |
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