National Centre for Register-Based Research, Aarhus University, 8210, Aarhus V, Denmark.
Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
Nat Commun. 2023 Feb 15;14(1):852. doi: 10.1038/s41467-023-36392-5.
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.
维生素 D 结合蛋白（DBP）由特异性成分（GC）基因编码，是维生素 D 系统的组成部分。我们对 65589 名新生儿的 DBP 浓度进行了全基因组关联研究，确定了 26 个独立的基因座，其中 17 个位于或靠近 GC 基因，精细映射确定了位于 12 号和 17 号染色体上的 2 个错义变异（分别位于 SH2B3 和 GSDMA 中）。当调整 GC 单倍型时，我们发现 10 号染色体上分布着 15 个独立的基因座。孟德尔随机化分析确定了 DBP 浓度升高与（a）25-羟维生素 D 浓度升高，以及（b）多发性硬化症和类风湿性关节炎风险降低之间的单向影响。全表型关联研究证实，较高的 DBP 浓度与维生素 D 缺乏症风险降低有关。我们的研究结果为 DBP 对维生素 D 状态和一系列健康结果的影响提供了有价值的见解。
