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

7 Citationer (Scopus)

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.

OriginalsprogEngelsk
Artikelnummer852
TidsskriftNature Communications
Vol/bind14
Udgave nummer1
Sider (fra-til)852
ISSN2041-1722
DOI
StatusUdgivet - dec. 2023

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