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 Sierra Cohen; Kristin Skogstrand; Naomi R. Wray; Joana A. Revez; Florian Privé; Liselotte Vogdrup Petersen; Cynthia Marie Bulik; Oleguer Plana‐Ripoll; Katherine Louise Musliner; Esben Agerbo; Anders Dupont Børglum; DAVID MICHAEL HOUGAARD; Merete Nordentoft; Thomas Mears Werge; Preben Bo Mortensen; Bjarni Jóhann Vilhjálmsson; John Joseph McGrath

doi:10.1038/s41467-023-36392-5

Genetic & Genomic MedicineNature CommunicationsFeb 15, 2023

Peer-reviewed journal article

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

Clara Albiñana iD, Zhihong Zhu iD, Nis Borbye‐Lorenzen iD, Sanne Grundvad Boelt iD, Arieh Sierra Cohen iD, Kristin Skogstrand iD, Naomi R. Wray iD, Joana A. Revez iD, Florian Privé iD, Liselotte Vogdrup Petersen iD, Cynthia Marie Bulik iD, Oleguer Plana‐Ripoll iD, Katherine Louise Musliner iD, Esben Agerbo iD, Anders Dupont Børglum iD, DAVID MICHAEL HOUGAARD iD, Merete Nordentoft iD, Thomas Mears Werge iD, Preben Bo Mortensen iD, Bjarni Jóhann Vilhjálmsson iD, John Joseph McGrath iD

Abstract

The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a much-studied component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates, we identified 26 independent loci, 17 of which were in or close to the GC gene, with fine-mapping identifying 2 loci on chromosomes 12 and 17 (missense variants within SH2B3 and GSDMA, respectively). When adjusted for key GC haplotypes, we found 15 independent loci distributed over 10 chromosomes. Mendelian randomization analyses found evidence consistent with a unidirectional, causal effect of higher DBP concentration and (a) higher 25 hydroxyvitamin D (25OHD) concentration, and (b) a reduced risk of multiple sclerosis and rheumatoid arthritis. A phenome-wide association study in an external dataset confirmed that higher DBP concentration was associated with higher 25OHD concentration and a reduced risk of vitamin D deficiency. Our study provides new insights into the influence of DBP on vitamin D status and a range of health outcomes.

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