Higher Vitamin D-binding protein is good (neonates in this case)

Created February 2023

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.

Clara Albiñana 1, Zhihong Zhu 1, Nis Borbye-Lorenzen 2, Sanne Grundvad Boelt 2 3, Arieh S Cohen 4, Kristin Skogstrand 2, Naomi R Wray 5 6, Joana A Revez 5, Florian Privé 1, Liselotte V Petersen 1 7, Cynthia M Bulik 8 9 10, Oleguer Plana-Ripoll 1 11, Katherine L Musliner 12, 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

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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.

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Grant support

na/Danmarks Grundforskningsfond (Danish National Research Foundation)

R345-2020-1588/Lundbeckfonden (Lundbeck Foundation)

R102-A9118, R155-2014-1724, and R248-2017-2003/Lundbeckfonden (Lundbeck Foundation)

R276-2018-4581/Lundbeckfonden (Lundbeck Foundation)

R335-2019-2339/Lundbeckfonden (Lundbeck Foundation)

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