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在全基因组关联研究时代理解维生素状态生物标志物的遗传结构:生物学见解与临床意义

Understanding the Genetic Architecture of Vitamin Status Biomarkers in the Genome-Wide Association Study Era: Biological Insights and Clinical Significance.

作者信息

Reay William R, Clarke Erin D, Albiñana Clara, Hwang Liang-Dar

机构信息

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.

出版信息

Adv Nutr. 2024 Dec;15(12):100344. doi: 10.1016/j.advnut.2024.100344. Epub 2024 Nov 16.


DOI:10.1016/j.advnut.2024.100344
PMID:39551434
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11653147/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b28/11653147/2fb89de2e929/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b28/11653147/0d0baa651592/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b28/11653147/5bf5333fb908/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b28/11653147/32ea335072c8/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b28/11653147/2fb89de2e929/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b28/11653147/0d0baa651592/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b28/11653147/5bf5333fb908/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b28/11653147/32ea335072c8/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b28/11653147/2fb89de2e929/gr4.jpg

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本文引用的文献

[1]
Non-linear Mendelian randomization: detection of biases using negative controls with a focus on BMI, Vitamin D and LDL cholesterol.

Eur J Epidemiol. 2024-5

[2]
Genetic influences on circulating retinol and its relationship to human health.

Nat Commun. 2024-2-19

[3]
Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome.

Brain. 2024-4-4

[4]
Vitamin C.

Adv Nutr. 2024-1

[5]
Scientific opinion on the tolerable upper intake level for folate.

EFSA J. 2023-11-13

[6]
Cross-ancestry analyses identify new genetic loci associated with 25-hydroxyvitamin D.

PLoS Genet. 2023-11

[7]
Causal effects of genetically vitamins and sepsis risk: a two-sample Mendelian randomization study.

BMC Infect Dis. 2023-11-7

[8]
Serum vitamin C status of people in New South Wales: retrospective analysis of findings at a public referral hospital.

Med J Aust. 2023-11-20

[9]
Comparison of the Effect of Daily Vitamin D2 and Vitamin D3 Supplementation on Serum 25-Hydroxyvitamin D Concentration (Total 25(OH)D, 25(OH)D2, and 25(OH)D3) and Importance of Body Mass Index: A Systematic Review and Meta-Analysis.

Adv Nutr. 2024-1

[10]
The effect of B-vitamins on the prevention and treatment of cardiovascular diseases: a systematic review and meta-analysis.

Nutr Rev. 2024-10-1

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