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推进转录组大数据科学时代的中风基因组研究:新出现的优先事项和机会。

Advancing stroke genomic research in the age of Trans-Omics big data science: Emerging priorities and opportunities.

机构信息

Center for Genomic and Precision Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria; Department of Medicine, University of Ibadan, Ibadan, Nigeria.

Center for Translation Research and Implementation Science, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

出版信息

J Neurol Sci. 2017 Nov 15;382:18-28. doi: 10.1016/j.jns.2017.09.021. Epub 2017 Sep 18.

Abstract

BACKGROUND

We systematically reviewed the genetic variants associated with stroke in genome-wide association studies (GWAS) and examined the emerging priorities and opportunities for rapidly advancing stroke research in the era of Trans-Omics science.

METHODS

Using the PRISMA guideline, we searched PubMed and NHGRI- EBI GWAS catalog for stroke studies from 2007 till May 2017.

RESULTS

We included 31 studies. The major challenge is that the few validated variants could not account for the full genetic risk of stroke and have not been translated for clinical use. None of the studies included continental Africans. Genomic study of stroke among Africans presents a unique opportunity for the discovery, validation, functional annotation, Trans-Omics study and translation of genomic determinants of stroke with implications for global populations. This is because all humans originated from Africa, a continent with a unique genomic architecture and a distinctive epidemiology of stroke; as well as substantially higher heritability and resolution of fine mapping of stroke genes.

CONCLUSION

Understanding the genomic determinants of stroke and the corresponding molecular mechanisms will revolutionize the development of a new set of precise biomarkers for stroke prediction, diagnosis and prognostic estimates as well as personalized interventions for reducing the global burden of stroke.

摘要

背景

我们系统地回顾了全基因组关联研究(GWAS)中与中风相关的遗传变异,并研究了在 Trans-Omics 科学时代快速推进中风研究的新重点和机遇。

方法

我们使用 PRISMA 指南,在 PubMed 和 NHGRI-EBI GWAS 目录中搜索了 2007 年至 2017 年 5 月期间的中风研究。

结果

我们纳入了 31 项研究。主要的挑战是,少数经过验证的变异并不能说明中风的全部遗传风险,也没有为临床应用所转化。没有一项研究包括非洲大陆的非洲人。对非洲人中的中风进行基因组研究为发现、验证、功能注释、Trans-Omics 研究以及中风基因组决定因素的转化提供了独特的机会,这对全球人口具有重要意义。这是因为所有人类都起源于非洲,非洲是一个具有独特基因组结构和独特中风流行病学的大陆;同时,中风基因的精细定位的遗传率和分辨率也有显著提高。

结论

了解中风的基因组决定因素及其相应的分子机制将彻底改变中风预测、诊断和预后估计以及减少全球中风负担的个性化干预措施的一整套精确生物标志物的发展。

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