Australian Centre for Precision Health, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia.
South Australian Health and Medical Research Institute, Adelaide, SA 5001, Australia.
Nutrients. 2022 Oct 20;14(20):4408. doi: 10.3390/nu14204408.
Twin studies suggest a considerable genetic contribution to the variability in 25-hydroxyvitamin D (25(OH)D) concentrations, reporting heritability estimates up to 80% in some studies. While genome-wide association studies (GWAS) suggest notably lower rates (13−16%), they have identified many independent variants that associate with serum 25(OH)D concentrations. These discoveries have provided some novel insight into the metabolic pathway, and in this review we outline findings from GWAS studies to date with a particular focus on 35 variants which have provided replicating evidence for an association with 25(OH)D across independent large-scale analyses. Some of the 25(OH)D associating variants are linked directly to the vitamin D metabolic pathway, while others may reflect differences in storage capacity, lipid metabolism, and pathways reflecting skin properties. By constructing a genetic score including these 25(OH)D associated variants we show that genetic differences in 25(OH)D concentrations persist across the seasons, and the odds of having low concentrations (<50 nmol/L) are about halved for individuals in the highest 20% of vitamin D genetic score compared to the lowest quintile, an impact which may have notable influences on retaining adequate levels. We also discuss recent studies on personalized approaches to vitamin D supplementation and show how Mendelian randomization studies can help inform public health strategies to reduce adverse health impacts of vitamin D deficiency.
双生子研究表明，25-羟维生素 D（25（OH）D）浓度的变异性存在相当大的遗传贡献，一些研究报告的遗传率估计高达 80%。虽然全基因组关联研究（GWAS）表明遗传率明显较低（13-16%），但它们已经确定了许多与血清 25（OH）D 浓度相关的独立变异。这些发现为代谢途径提供了一些新的见解，在这篇综述中，我们概述了迄今为止 GWAS 研究的发现，特别关注了 35 个变异体，这些变异体在独立的大规模分析中提供了与 25（OH）D 相关的复制证据。一些与 25（OH）D 相关的变异体直接与维生素 D 代谢途径有关，而其他变异体可能反映了储存能力、脂质代谢和反映皮肤特性的途径的差异。通过构建一个包含这些 25（OH）D 相关变异体的遗传评分，我们表明，25（OH）D 浓度的遗传差异在整个季节都存在，与最低五分位数相比，维生素 D 遗传评分最高的 20%个体的 25（OH）D 浓度较低（<50 nmol/L）的几率降低了约一半，这种影响可能对维持足够的水平有显著影响。我们还讨论了最近关于维生素 D 补充的个性化方法的研究，并展示了孟德尔随机化研究如何帮助为减少维生素 D 缺乏对健康的不利影响提供公共卫生策略。
