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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| Veröffentlicht in: | PloS one 2021-05, Vol.16 (5), p.e0251423-e0251423 |
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| creator | Palmer, Nicholette D Lu, Lingyi Register, Thomas C Lenchik, Leon Carr, J Jeffrey Hicks, Pamela J Smith, S Carrie Xu, Jianzhao Dimitrov, Latchezar Keaton, Jacob Guan, Meijian Ng, Maggie C Y Chen, Yii-der I Hanley, Anthony J Engelman, Corinne D Norris, Jill M Langefeld, Carl D Wagenknecht, Lynne E Bowden, Donald W Freedman, Barry I Divers, Jasmin |
| 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. |
| doi_str_mv | 10.1371/journal.pone.0251423 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0251423</identifier><identifier>PMID: 34014961</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>African Americans ; Aging ; Alfacalcidol ; Arteriosclerosis ; Atherosclerosis ; Biochemistry ; Biology and Life Sciences ; Biomedical materials ; Bone density ; Bone mineral density ; Bones ; Calcifediol ; Calciferol ; Calcification ; Calcium ; Calculi ; Chromatography ; Complications and side effects ; Density ; Development and progression ; Diabetes ; Diabetes mellitus ; Editing ; Epidemiology ; Ethnicity ; Funding ; Genetic aspects ; Genetics ; Genome-wide association studies ; Genomes ; Genomics ; Glucose ; Health aspects ; Health care facilities ; Health sciences ; Mass spectrometry ; Measurement ; Medical innovations ; Medicine ; Medicine and Health Sciences ; Metabolism ; Metabolites ; Minority & ethnic groups ; Nephrolithiasis ; Osteoporosis ; Pediatrics ; People and places ; Physical sciences ; Physiological aspects ; Precision medicine ; Public health ; Radiology ; Reviews ; Risk factors ; Scientific imaging ; Type 2 diabetes ; Vitamin D ; Vitamin D metabolism ; Vitamin metabolism</subject><ispartof>PloS one, 2021-05, Vol.16 (5), p.e0251423-e0251423</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Palmer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Palmer et al 2021 Palmer et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-66a05e65b040b5e14a1726b68dd9a7e45409de6e71bbfcb52e422cf63f3ba84e3</citedby><cites>FETCH-LOGICAL-c692t-66a05e65b040b5e14a1726b68dd9a7e45409de6e71bbfcb52e422cf63f3ba84e3</cites><orcidid>0000-0001-8883-2511</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136717/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136717/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34014961$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Qu, Hui-Qi</contributor><creatorcontrib>Palmer, Nicholette D</creatorcontrib><creatorcontrib>Lu, Lingyi</creatorcontrib><creatorcontrib>Register, Thomas C</creatorcontrib><creatorcontrib>Lenchik, Leon</creatorcontrib><creatorcontrib>Carr, J Jeffrey</creatorcontrib><creatorcontrib>Hicks, Pamela J</creatorcontrib><creatorcontrib>Smith, S Carrie</creatorcontrib><creatorcontrib>Xu, Jianzhao</creatorcontrib><creatorcontrib>Dimitrov, Latchezar</creatorcontrib><creatorcontrib>Keaton, Jacob</creatorcontrib><creatorcontrib>Guan, Meijian</creatorcontrib><creatorcontrib>Ng, Maggie C Y</creatorcontrib><creatorcontrib>Chen, Yii-der I</creatorcontrib><creatorcontrib>Hanley, Anthony J</creatorcontrib><creatorcontrib>Engelman, Corinne D</creatorcontrib><creatorcontrib>Norris, Jill M</creatorcontrib><creatorcontrib>Langefeld, Carl D</creatorcontrib><creatorcontrib>Wagenknecht, Lynne E</creatorcontrib><creatorcontrib>Bowden, Donald W</creatorcontrib><creatorcontrib>Freedman, Barry I</creatorcontrib><creatorcontrib>Divers, Jasmin</creatorcontrib><title>Genome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>African Americans</subject><subject>Aging</subject><subject>Alfacalcidol</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Biochemistry</subject><subject>Biology and Life Sciences</subject><subject>Biomedical materials</subject><subject>Bone density</subject><subject>Bone mineral density</subject><subject>Bones</subject><subject>Calcifediol</subject><subject>Calciferol</subject><subject>Calcification</subject><subject>Calcium</subject><subject>Calculi</subject><subject>Chromatography</subject><subject>Complications and side effects</subject><subject>Density</subject><subject>Development and progression</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Editing</subject><subject>Epidemiology</subject><subject>Ethnicity</subject><subject>Funding</subject><subject>Genetic aspects</subject><subject>Genetics</subject><subject>Genome-wide association studies</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Glucose</subject><subject>Health aspects</subject><subject>Health care facilities</subject><subject>Health sciences</subject><subject>Mass spectrometry</subject><subject>Measurement</subject><subject>Medical innovations</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Minority & ethnic groups</subject><subject>Nephrolithiasis</subject><subject>Osteoporosis</subject><subject>Pediatrics</subject><subject>People and places</subject><subject>Physical sciences</subject><subject>Physiological aspects</subject><subject>Precision medicine</subject><subject>Public health</subject><subject>Radiology</subject><subject>Reviews</subject><subject>Risk factors</subject><subject>Scientific imaging</subject><subject>Type 2 diabetes</subject><subject>Vitamin D</subject><subject>Vitamin D metabolism</subject><subject>Vitamin 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Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Palmer, Nicholette D</au><au>Lu, Lingyi</au><au>Register, Thomas C</au><au>Lenchik, Leon</au><au>Carr, J Jeffrey</au><au>Hicks, Pamela J</au><au>Smith, S Carrie</au><au>Xu, Jianzhao</au><au>Dimitrov, Latchezar</au><au>Keaton, Jacob</au><au>Guan, Meijian</au><au>Ng, Maggie C Y</au><au>Chen, Yii-der I</au><au>Hanley, Anthony J</au><au>Engelman, Corinne D</au><au>Norris, Jill M</au><au>Langefeld, Carl D</au><au>Wagenknecht, Lynne E</au><au>Bowden, Donald W</au><au>Freedman, Barry I</au><au>Divers, Jasmin</au><au>Qu, Hui-Qi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-05-20</date><risdate>2021</risdate><volume>16</volume><issue>5</issue><spage>e0251423</spage><epage>e0251423</epage><pages>e0251423-e0251423</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34014961</pmid><doi>10.1371/journal.pone.0251423</doi><tpages>e0251423</tpages><orcidid>https://orcid.org/0000-0001-8883-2511</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2021-05, Vol.16 (5), p.e0251423-e0251423 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2529908461 |
| source | PubMed Central Free; Public Library of Science; DOAJ Directory of Open Access Journals; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | African Americans Aging Alfacalcidol Arteriosclerosis Atherosclerosis Biochemistry Biology and Life Sciences Biomedical materials Bone density Bone mineral density Bones Calcifediol Calciferol Calcification Calcium Calculi Chromatography Complications and side effects Density Development and progression Diabetes Diabetes mellitus Editing Epidemiology Ethnicity Funding Genetic aspects Genetics Genome-wide association studies Genomes Genomics Glucose Health aspects Health care facilities Health sciences Mass spectrometry Measurement Medical innovations Medicine Medicine and Health Sciences Metabolism Metabolites Minority & ethnic groups Nephrolithiasis Osteoporosis Pediatrics People and places Physical sciences Physiological aspects Precision medicine Public health Radiology Reviews Risk factors Scientific imaging Type 2 diabetes Vitamin D Vitamin D metabolism Vitamin metabolism |
| title | Genome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study |
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