While it is known that vitamin D deficiency is associated with adverse bone outcomes, it remains unclear whether low vitamin D status may increase the risk of a wider range of health outcomes. We had the opportunity to explore the association between common genetic variants associated with both 25 hydroxyvitamin D (25OHD) and the vitamin D binding protein (DBP, encoded by the GC gene) with a comprehensive range of health disorders and laboratory tests in a large academic medical center. We used summary statistics for 25OHD and DBP to generate polygenic scores (PGS) for 66,482 participants with primarily European ancestry and 13,285 participants with primarily African ancestry from the Vanderbilt University Medical Center Biobank (BioVU). We examined the predictive properties of PGS25OHD, and two scores related to DBP concentration with respect to 1322 health-related phenotypes and 315 laboratory-measured phenotypes from electronic health records. In those with European ancestry: (a) the PGS25OHD and PGSDBP scores, and individual SNPs rs4588 and rs7041 were associated with both 25OHD concentration and 1,25 dihydroxyvitamin D concentrations; (b) higher PGS25OHD was associated with decreased concentrations of triglycerides and cholesterol, and reduced risks of vitamin D deficiency, disorders of lipid metabolism, and diabetes. In general, the findings for the African ancestry group were consistent with findings from the European ancestry analyses. Our study confirms the utility of PGS and two key variants within the GC gene (rs4588 and rs7041) to predict the risk of vitamin D deficiency in clinical settings and highlights the shared biology between vitamin D-related genetic pathways a range of health outcomes.

中文翻译：

---

与 25 羟基维生素 D 浓度和维生素 D 结合蛋白浓度的遗传相关性相关的健康结果的全表型关联研究

虽然众所周知，维生素 D 缺乏与骨骼不良结果相关，但尚不清楚维生素 D 水平低是否会增加更广泛健康结果的风险。我们有机会探索与 25 羟基维生素 D (25OHD) 和维生素 D 结合蛋白 (DBP，由GC基因），在大型学术医疗中心提供全面的健康疾病和实验室测试。我们使用 25OHD 和 DBP 的汇总统计数据，为来自范德比尔特大学医学中心生物库 (BioVU) 的 66,482 名主要是欧洲血统的参与者和 13,285 名主要是非洲血统的参与者生成多基因评分 (PGS)。我们检查了 PGS 的预测特性25OHD，以及与来自电子健康记录的 1322 个健康相关表型和 315 个实验室测量表型有关的 DBP 浓度相关的两个分数。对于有欧洲血统的人： (a) PGS25OHD和PGS舒张压评分，并且各个 SNP rs4588 和 rs7041 与 25OHD 浓度和 1,25 二羟基维生素 D 浓度相关； (b) 更高的 PGS25OHD与甘油三酯和胆固醇浓度降低有关，并降低维生素 D 缺乏、脂质代谢紊乱和糖尿病的风险。总体而言，非洲血统群体的研究结果与欧洲血统分析的结果一致。我们的研究证实了 PGS 的实用性以及其中的两个关键变体GC基因（rs4588 和 rs7041）来预测临床环境中维生素 D 缺乏的风险，并强调维生素 D 相关遗传途径与一系列健康结果之间的共享生物学。