Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots

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

doi:10.1038/s41467-023-36392-5

Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots

Nat Commun. 2023 Feb 15;14(1):852. doi: 10.1038/s41467-023-36392-5.

Authors

Clara Albiñana¹, Zhihong Zhu¹, Nis Borbye-Lorenzen², Sanne Grundvad Boelt^{2

3}, Arieh S Cohen⁴, Kristin Skogstrand², Naomi R Wray^{5

6}, Joana A Revez⁵, Florian Privé¹, Liselotte V Petersen^{1

7}, Cynthia M Bulik^{8

9

10}, Oleguer Plana-Ripoll^{1

11}, Katherine L Musliner¹², Esben Agerbo^{1

7

13}, Anders D Børglum^{7

14

15}, David M Hougaard^{7

16}, Merete Nordentoft^{7

17

18}, Thomas Werge^{7

19

20

21}, Preben Bo Mortensen^{1

7

13}, Bjarni J Vilhjálmsson^{1

7

22}, John J McGrath^{23

24

25}

Affiliations

¹ National Centre for Register-Based Research, Aarhus University, 8210, Aarhus V, Denmark.
² Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
³ Clinical Mass Spectrometry, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark.
⁴ Testcenter Denmark, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark.
⁵ Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
⁶ Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
⁷ The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8210, Aarhus V, Denmark.
⁸ Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
¹⁰ Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹¹ Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, 8200, Aarhus N, Denmark.
¹² Department of Affective Disorders, Aarhus University and Aarhus University Hospital-Psychiatry, Aarhus, Denmark.
¹³ CIRRAU - Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
¹⁴ Center for Genomics and Personalized Medicine, Aarhus University, Aarhus, Denmark.
¹⁵ Department of Biomedicine and the iSEQ Center, Aarhus University, Aarhus, Denmark.
¹⁶ Department for Congenital Disorders, Statens Serum Institut, 2300, Copenhagen S, Denmark.
¹⁷ Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, 2100, Copenhagen, Denmark.
¹⁸ Department of Clinical Medicine, University of Copenhagen, 2200, Copenhagen N, Denmark.
¹⁹ Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, Copenhagen N, Denmark.
²⁰ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
²¹ Lundbeck Center for Geogenetics, GLOBE Institute, University of Copenhagen, Copenhagen, Denmark.
²² Bioinformatics Research Centre, Aarhus University, 8000, Aarhus C, Denmark.
²³ National Centre for Register-Based Research, Aarhus University, 8210, Aarhus V, Denmark. [email protected].
²⁴ Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia. [email protected].
²⁵ Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Brisbane, QLD, 4076, Australia. [email protected].

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Calcifediol
Genome-Wide Association Study*
Humans
Infant, Newborn
Polymorphism, Single Nucleotide
Pore Forming Cytotoxic Proteins / genetics
Vitamin D / genetics
Vitamin D-Binding Protein* / genetics
Vitamins

Substances

25-hydroxyvitamin D
Vitamin D-Binding Protein
Vitamin D
Calcifediol
Vitamins
GSDMA protein, human
Pore Forming Cytotoxic Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding