Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots
Abstract The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates we identify 26 independent loci, 17 of which are in or close to the GC gene, with fine-m...
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| Format: | Article |
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Nature Portfolio
2023-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-36392-5 |
| _version_ | 1827326970018398208 |
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| author | Clara Albiñana Zhihong Zhu Nis Borbye-Lorenzen Sanne Grundvad Boelt Arieh S. Cohen Kristin Skogstrand Naomi R. Wray Joana A. Revez Florian Privé Liselotte V. Petersen Cynthia M. Bulik Oleguer Plana-Ripoll Katherine L. Musliner Esben Agerbo Anders D. Børglum David M. Hougaard Merete Nordentoft Thomas Werge Preben Bo Mortensen Bjarni J. Vilhjálmsson John J. McGrath |
| author_facet | Clara Albiñana Zhihong Zhu Nis Borbye-Lorenzen Sanne Grundvad Boelt Arieh S. Cohen Kristin Skogstrand Naomi R. Wray Joana A. Revez Florian Privé Liselotte V. Petersen Cynthia M. Bulik Oleguer Plana-Ripoll Katherine L. Musliner Esben Agerbo Anders D. Børglum David M. Hougaard Merete Nordentoft Thomas Werge Preben Bo Mortensen Bjarni J. Vilhjálmsson John J. McGrath |
| author_sort | Clara Albiñana |
| collection | DOAJ |
| description | Abstract The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates we identify 26 independent loci, 17 of which are in or close to the GC gene, with fine-mapping identifying 2 missense variants on chromosomes 12 and 17 (within SH2B3 and GSDMA, respectively). When adjusted for GC haplotypes, we find 15 independent loci distributed over 10 chromosomes. Mendelian randomization analyses identify a unidirectional effect of higher DBP concentration and (a) higher 25-hydroxyvitamin D concentration, and (b) a reduced risk of multiple sclerosis and rheumatoid arthritis. A phenome-wide association study confirms that higher DBP concentration is associated with a reduced risk of vitamin D deficiency. Our findings provide valuable insights into the influence of DBP on vitamin D status and a range of health outcomes. |
| first_indexed | 2024-03-07T14:54:09Z |
| format | Article |
| id | doaj.art-15845a4d45ac43fd9c945f9f49a9c9cc |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:54:09Z |
| publishDate | 2023-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-15845a4d45ac43fd9c945f9f49a9c9cc2024-03-05T19:30:55ZengNature PortfolioNature Communications2041-17232023-02-0114111610.1038/s41467-023-36392-5Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spotsClara Albiñana0Zhihong Zhu1Nis Borbye-Lorenzen2Sanne Grundvad Boelt3Arieh S. Cohen4Kristin Skogstrand5Naomi R. Wray6Joana A. Revez7Florian Privé8Liselotte V. Petersen9Cynthia M. Bulik10Oleguer Plana-Ripoll11Katherine L. Musliner12Esben Agerbo13Anders D. Børglum14David M. Hougaard15Merete Nordentoft16Thomas Werge17Preben Bo Mortensen18Bjarni J. Vilhjálmsson19John J. McGrath20National Centre for Register-Based Research, Aarhus UniversityNational Centre for Register-Based Research, Aarhus UniversityCenter for Neonatal Screening, Department of Congenital Disorders, Statens Serum InstitutCenter for Neonatal Screening, Department of Congenital Disorders, Statens Serum InstitutTestcenter Denmark, Statens Serum InstitutCenter for Neonatal Screening, Department of Congenital Disorders, Statens Serum InstitutInstitute for Molecular Bioscience, University of QueenslandInstitute for Molecular Bioscience, University of QueenslandNational Centre for Register-Based Research, Aarhus UniversityNational Centre for Register-Based Research, Aarhus UniversityDepartment of Psychiatry, University of North Carolina at Chapel HillNational Centre for Register-Based Research, Aarhus UniversityDepartment of Affective Disorders, Aarhus University and Aarhus University Hospital-PsychiatryNational Centre for Register-Based Research, Aarhus UniversityThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCHThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCHThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCHThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCHNational Centre for Register-Based Research, Aarhus UniversityNational Centre for Register-Based Research, Aarhus UniversityNational Centre for Register-Based Research, Aarhus UniversityAbstract The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates we identify 26 independent loci, 17 of which are in or close to the GC gene, with fine-mapping identifying 2 missense variants on chromosomes 12 and 17 (within SH2B3 and GSDMA, respectively). When adjusted for GC haplotypes, we find 15 independent loci distributed over 10 chromosomes. Mendelian randomization analyses identify a unidirectional effect of higher DBP concentration and (a) higher 25-hydroxyvitamin D concentration, and (b) a reduced risk of multiple sclerosis and rheumatoid arthritis. A phenome-wide association study confirms that higher DBP concentration is associated with a reduced risk of vitamin D deficiency. Our findings provide valuable insights into the influence of DBP on vitamin D status and a range of health outcomes.https://doi.org/10.1038/s41467-023-36392-5 |
| spellingShingle | Clara Albiñana Zhihong Zhu Nis Borbye-Lorenzen Sanne Grundvad Boelt Arieh S. Cohen Kristin Skogstrand Naomi R. Wray Joana A. Revez Florian Privé Liselotte V. Petersen Cynthia M. Bulik Oleguer Plana-Ripoll Katherine L. Musliner Esben Agerbo Anders D. Børglum David M. Hougaard Merete Nordentoft Thomas Werge Preben Bo Mortensen Bjarni J. Vilhjálmsson John J. McGrath Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots Nature Communications |
| title | Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots |
| title_full | Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots |
| title_fullStr | Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots |
| title_full_unstemmed | Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots |
| title_short | Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots |
| title_sort | genetic correlates of vitamin d binding protein and 25 hydroxyvitamin d in neonatal dried blood spots |
| url | https://doi.org/10.1038/s41467-023-36392-5 |
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