Reay William R, Clarke Erin D, Albiñana Clara, Hwang Liang-Dar
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
Food and Nutrition Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia; School of Health Sciences, the University of Newcastle, University Drive, Callaghan, NSW, Australia.
Adv Nutr. 2024 Dec;15(12):100344. doi: 10.1016/j.advnut.2024.100344. Epub 2024 Nov 16.
Vitamins play an intrinsic role in human health and are targets for clinical intervention through dietary or pharmacological approaches. Biomarkers of vitamin status are complex traits, measurable phenotypes that arise from an interplay between dietary and other environmental factors with a genetic component that is polygenic, meaning many genes are plausibly involved. Studying these genetic influences will improve our knowledge of fundamental vitamin biochemistry, refine estimates of the effects of vitamins on human health, and may in future prove clinically actionable. Here, we evaluate genetic studies of circulating and excreted biomarkers of vitamin status in the era of hypothesis-free genome-wide association studies (GWAS) that have provided unprecedented insights into the genetic architecture of these traits. We found that the most comprehensive and well-powered GWAS currently available were for circulating status biomarkers of vitamin A, C, D, and a subset of the B vitamins (B and B). The biology implicated by GWAS of measured biomarkers of each vitamin is then discussed, both in terms of key genes and higher-order processes. Across all major vitamins, there were genetic signals revealed by GWAS that could be directly linked with known vitamin biochemistry. We also outline how genetic variants associated with vitamin status biomarkers have been already extensively used to estimate causal effects of vitamins on human health outcomes, which is particularly important given the large number of randomized control trials of vitamin related interventions with null findings. Finally, we discuss the current evidence for the clinical applicability of findings from vitamin GWAS, along with future directions for the field to maximize the utility of these data.
维生素在人类健康中发挥着内在作用,并且是通过饮食或药理学方法进行临床干预的目标。维生素状态的生物标志物是复杂的性状,是可测量的表型,它们源于饮食和其他环境因素与多基因遗传成分之间的相互作用,这意味着可能涉及许多基因。研究这些遗传影响将增进我们对基本维生素生物化学的了解,完善对维生素对人类健康影响的估计,并且未来可能在临床上得到应用。在这里,我们评估了在无假设全基因组关联研究(GWAS)时代对维生素状态的循环和排泄生物标志物的遗传研究,这些研究为这些性状的遗传结构提供了前所未有的见解。我们发现,目前可用的最全面且效力最强的GWAS是针对维生素A、C、D以及一部分B族维生素(B1和B2)的循环状态生物标志物。然后从关键基因和高阶过程两方面讨论了每种维生素的测量生物标志物的GWAS所涉及的生物学。在所有主要维生素中,GWAS揭示的遗传信号都可以直接与已知的维生素生物化学联系起来。我们还概述了与维生素状态生物标志物相关的遗传变异如何已经被广泛用于估计维生素对人类健康结果的因果效应,鉴于大量维生素相关干预的随机对照试验结果为阴性,这一点尤为重要。最后,我们讨论了维生素GWAS研究结果临床适用性的当前证据,以及该领域为最大限度利用这些数据的未来方向。
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