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20 万英国生物库参与者的药物反应遗传药理学。

Drug Response Pharmacogenetics for 200,000 UK Biobank Participants.

机构信息

Biomedical Informatics, Stanford University, 450 Serra Mall, Stanford, CA 94305, United States of America,

出版信息

Pac Symp Biocomput. 2021;26:184-195.

Abstract

Pharmacogenetics studies how genetic variation leads to variability in drug response. Guidelines for selecting the right drug and right dose for patients based on their genetics are clinically effective, but are widely unused. For some drugs, the normal clinical decision making process may lead to the optimal dose of a drug that minimizes side effects and maximizes effectiveness. Without measurements of genotype, physicians and patients may adjust dosage in a manner that reflects the underlying genetics. The emergence of genetic data linked to longitudinal clinical data in large biobanks offers an opportunity to confirm known pharmacogenetic interactions as well as discover novel associations by investigating outcomes from normal clinical practice. Here we use the UK Biobank to search for pharmacogenetic interactions among 200 drugs and 9 genes among 200,000 participants. We identify associations between pharmacogene phenotypes and drug maintenance dose as well as differential drug response phenotypes. We find support for several known drug-gene associations as well as novel pharmacogenetic interactions.

摘要

药物遗传学研究遗传变异如何导致药物反应的变异性。根据患者的遗传学信息为其选择合适药物和剂量的指南在临床上是有效的,但尚未得到广泛应用。对于某些药物,正常的临床决策过程可能会导致药物的最佳剂量,从而最大限度地减少副作用并提高疗效。如果没有基因型的测量,医生和患者可能会以反映潜在遗传学的方式调整剂量。大型生物库中与纵向临床数据相关的遗传数据的出现为通过调查正常临床实践中的结果来确认已知的药物遗传学相互作用以及发现新的关联提供了机会。在这里,我们使用英国生物库在 20 万名参与者中搜索 200 种药物和 9 个基因之间的药物遗传学相互作用。我们确定了药物基因表型与药物维持剂量以及药物反应表型差异之间的关联。我们发现了一些已知的药物-基因关联以及新的药物遗传学相互作用的支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1f/7951365/a37847029f1c/nihms-1649362-f0001.jpg

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