Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots
oleh: 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
| Format: | Article |
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| Diterbitkan: | Nature Portfolio 2023-02-01 |
Deskripsi
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.