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

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 VilhjálmssonJohn J McGrath^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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.

Original language	English
Article number	852
Journal	Nature Communications
Volume	14
Issue	1
Number of pages	16
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-023-36392-5
Publication status	Published - Feb 2023

Keywords

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

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Albiñana, C., Zhu, Z., Borbye-Lorenzen, N., Boelt, S. G., Cohen, A. S., Skogstrand, K., Wray, N. R., Revez, J. A., Privé, F., Petersen, L. V., Bulik, C. M., Plana-Ripoll, O., Musliner, K. L., Agerbo, E., Børglum, A. D., Hougaard, D. M., Nordentoft, M., Werge, T., Mortensen, P. B., ... McGrath, J. J. (2023). Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots. Nature Communications, 14(1), Article 852. https://doi.org/10.1038/s41467-023-36392-5

@article{efd115d988f74e308aa2438480ae464b,

title = "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-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.",

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

author = "Clara Albi{\~n}ana and Zhihong Zhu and Nis Borbye-Lorenzen and Boelt, {Sanne Grundvad} and Cohen, {Arieh S} and Kristin Skogstrand and Wray, {Naomi R} and Revez, {Joana A} and Florian Priv{\'e} and Petersen, {Liselotte V} and Bulik, {Cynthia M} and Oleguer Plana-Ripoll and Musliner, {Katherine L} and Esben Agerbo and B{\o}rglum, {Anders D} and Hougaard, {David M} and Merete Nordentoft and Thomas Werge and Mortensen, {Preben Bo} and Vilhj{\'a}lmsson, {Bjarni J} and McGrath, {John J}",

year = "2023",

month = feb,

doi = "10.1038/s41467-023-36392-5",

language = "English",

volume = "14",

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Albiñana, C , Zhu, Z, Borbye-Lorenzen, N, Boelt, SG, Cohen, AS, Skogstrand, K, Wray, NR, Revez, JA, Privé, F , Petersen, LV, Bulik, CM, Plana-Ripoll, O , Musliner, KL , Agerbo, E , Børglum, AD, Hougaard, DM, Nordentoft, M, Werge, T, Mortensen, PB , Vilhjálmsson, BJ & McGrath, JJ 2023, 'Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots', Nature Communications, vol. 14, no. 1, 852. https://doi.org/10.1038/s41467-023-36392-5

Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots. / Albiñana, Clara ; Zhu, Zhihong; Borbye-Lorenzen, Nis et al.
In: Nature Communications, Vol. 14, No. 1, 852, 02.2023.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots

AU - Albiñana, Clara

AU - Zhu, Zhihong

AU - Borbye-Lorenzen, Nis

AU - Boelt, Sanne Grundvad

AU - Cohen, Arieh S

AU - Skogstrand, Kristin

AU - Wray, Naomi R

AU - Revez, Joana A

AU - Privé, Florian

AU - Petersen, Liselotte V

AU - Bulik, Cynthia M

AU - Plana-Ripoll, Oleguer

AU - Musliner, Katherine L

AU - Agerbo, Esben

AU - Børglum, Anders D

AU - Hougaard, David M

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - Mortensen, Preben Bo

AU - Vilhjálmsson, Bjarni J

AU - McGrath, John J

PY - 2023/2

Y1 - 2023/2

N2 - 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.

AB - 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.

KW - Infant, Newborn

KW - Humans

KW - Vitamin D-Binding Protein/genetics

KW - Genome-Wide Association Study

KW - Vitamin D/genetics

KW - Calcifediol

KW - Vitamins

KW - Polymorphism, Single Nucleotide

KW - Pore Forming Cytotoxic Proteins/genetics

UR - http://www.scopus.com/inward/record.url?scp=85148115127&partnerID=8YFLogxK

U2 - 10.1038/s41467-023-36392-5

DO - 10.1038/s41467-023-36392-5

M3 - Journal article

C2 - 36792583

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 852

ER -

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

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