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.

In this study the authors measure the concentration of 25-hydroxyvitamin D and vitamin D binding protein (DBP) in 65,589 neonatal dried blood samples. Findings from further analyses include that the genetic correlates of DBP concentration predict the risk of vitamin D deficiency.

Details

Title
Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots
Author
Albiñana, Clara 1   VIAFID ORCID Logo  ; Zhu, Zhihong 1   VIAFID ORCID Logo  ; Borbye-Lorenzen, Nis 2   VIAFID ORCID Logo  ; Boelt, Sanne Grundvad 3 ; Cohen, Arieh S. 4 ; Skogstrand, Kristin 2   VIAFID ORCID Logo  ; Wray, Naomi R. 5   VIAFID ORCID Logo  ; Revez, Joana A. 6   VIAFID ORCID Logo  ; Privé, Florian 1 ; Petersen, Liselotte V. 7   VIAFID ORCID Logo  ; Bulik, Cynthia M. 8   VIAFID ORCID Logo  ; Plana-Ripoll, Oleguer 9 ; Musliner, Katherine L. 10 ; Agerbo, Esben 11   VIAFID ORCID Logo  ; Børglum, Anders D. 12   VIAFID ORCID Logo  ; Hougaard, David M. 13   VIAFID ORCID Logo  ; Nordentoft, Merete 14 ; Werge, Thomas 15   VIAFID ORCID Logo  ; Mortensen, Preben Bo 11 ; Vilhjálmsson, Bjarni J. 16   VIAFID ORCID Logo  ; McGrath, John J. 17   VIAFID ORCID Logo 

1  Aarhus University, National Centre for Register-Based Research, Aarhus V, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
2  Statens Serum Institut, Center for Neonatal Screening, Department of Congenital Disorders, Copenhagen, Denmark (GRID:grid.6203.7) (ISNI:0000 0004 0417 4147) 
3  Statens Serum Institut, Center for Neonatal Screening, Department of Congenital Disorders, Copenhagen, Denmark (GRID:grid.6203.7) (ISNI:0000 0004 0417 4147); Statens Serum Institut, Clinical Mass Spectrometry, Copenhagen S, Denmark (GRID:grid.6203.7) (ISNI:0000 0004 0417 4147) 
4  Testcenter Denmark, Statens Serum Institut, Copenhagen S, Denmark (GRID:grid.6203.7) (ISNI:0000 0004 0417 4147) 
5  University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); University of Queensland, Queensland Brain Institute, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
6  University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
7  Aarhus University, National Centre for Register-Based Research, Aarhus V, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus V, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300) 
8  University of North Carolina at Chapel Hill, Department of Psychiatry, Chapel Hill, USA (GRID:grid.10698.36) (ISNI:0000 0001 2248 3208); Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); University of North Carolina at Chapel Hill, Department of Nutrition, Chapel Hill, USA (GRID:grid.10698.36) (ISNI:0000 0001 2248 3208) 
9  Aarhus University, National Centre for Register-Based Research, Aarhus V, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); Aarhus University and Aarhus University Hospital, Department of Clinical Epidemiology, Aarhus N, Denmark (GRID:grid.154185.c) (ISNI:0000 0004 0512 597X) 
10  Aarhus University and Aarhus University Hospital-Psychiatry, Department of Affective Disorders, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
11  Aarhus University, National Centre for Register-Based Research, Aarhus V, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus V, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Aarhus University, CIRRAU - Centre for Integrated Register-based Research, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
12  The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus V, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Aarhus University, Center for Genomics and Personalized Medicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); Aarhus University, Department of Biomedicine and the iSEQ Center, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
13  The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus V, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Statens Serum Institut, Department for Congenital Disorders, Copenhagen S, Denmark (GRID:grid.6203.7) (ISNI:0000 0004 0417 4147) 
14  The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus V, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); University of Copenhagen, Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X); University of Copenhagen, Department of Clinical Medicine, Copenhagen N, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X) 
15  The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus V, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Copenhagen University Hospital, Institute of Biological Psychiatry, Mental Health Services, Copenhagen N, Denmark (GRID:grid.4973.9) (ISNI:0000 0004 0646 7373); University of Copenhagen, Department of Clinical Medicine, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X); University of Copenhagen, Lundbeck Center for Geogenetics, GLOBE Institute, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X) 
16  Aarhus University, National Centre for Register-Based Research, Aarhus V, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus V, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Aarhus University, Bioinformatics Research Centre, Aarhus C, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
17  Aarhus University, National Centre for Register-Based Research, Aarhus V, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); University of Queensland, Queensland Brain Institute, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); The Park Centre for Mental Health, Queensland Centre for Mental Health Research, Brisbane, Australia (GRID:grid.417162.7) (ISNI:0000 0004 0606 3563) 
Pages
852
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-023-36392-5
ProQuest document ID
2776891962
Copyright
© The Author(s) 2023. corrected publication 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.