Genome-wide association testing beyond SNPs

IF 39.1 1区 生物学 Q1 GENETICS & HEREDITY
Laura Harris, Ellen M. McDonagh, Xiaolei Zhang, Katherine Fawcett, Amy Foreman, Petr Daneck, Panagiotis I. Sergouniotis, Helen Parkinson, Francesco Mazzarotto, Michael Inouye, Edward J. Hollox, Ewan Birney, Tomas Fitzgerald
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Abstract

Decades of genetic association testing in human cohorts have provided important insights into the genetic architecture and biological underpinnings of complex traits and diseases. However, for certain traits, genome-wide association studies (GWAS) for common SNPs are approaching signal saturation, which underscores the need to explore other types of genetic variation to understand the genetic basis of traits and diseases. Copy number variation (CNV) is an important source of heritability that is well known to functionally affect human traits. Recent technological and computational advances enable the large-scale, genome-wide evaluation of CNVs, with implications for downstream applications such as polygenic risk scoring and drug target identification. Here, we review the current state of CNV-GWAS, discuss current limitations in resource infrastructure that need to be overcome to enable the wider uptake of CNV-GWAS results, highlight emerging opportunities and suggest guidelines and standards for future GWAS for genetic variation beyond SNPs at scale.

Abstract Image

超越 SNP 的全基因组关联测试
几十年来,人类队列中的遗传关联测试为复杂性状和疾病的遗传结构和生物学基础提供了重要见解。然而,对于某些性状,针对常见 SNPs 的全基因组关联研究(GWAS)已接近信号饱和,这突出表明有必要探索其他类型的遗传变异,以了解性状和疾病的遗传基础。众所周知,拷贝数变异(CNV)是遗传性的一个重要来源,会对人类性状产生功能性影响。最近的技术和计算技术进步使得对 CNV 进行大规模全基因组评估成为可能,这对多基因风险评分和药物靶点鉴定等下游应用具有重要意义。在此,我们回顾了 CNV-GWAS 的现状,讨论了为使 CNV-GWAS 的结果得到更广泛的应用而需要克服的资源基础设施方面的限制,强调了新出现的机遇,并为未来针对 SNPs 以外的遗传变异进行大规模 GWAS 提出了指导原则和标准。
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来源期刊
Nature Reviews Genetics
Nature Reviews Genetics 生物-遗传学
CiteScore
57.40
自引率
0.50%
发文量
113
审稿时长
6-12 weeks
期刊介绍: At Nature Reviews Genetics, our goal is to be the leading source of reviews and commentaries for the scientific communities we serve. We are dedicated to publishing authoritative articles that are easily accessible to our readers. We believe in enhancing our articles with clear and understandable figures, tables, and other display items. Our aim is to provide an unparalleled service to authors, referees, and readers, and we are committed to maximizing the usefulness and impact of each article we publish. Within our journal, we publish a range of content including Research Highlights, Comments, Reviews, and Perspectives that are relevant to geneticists and genomicists. With our broad scope, we ensure that the articles we publish reach the widest possible audience. As part of the Nature Reviews portfolio of journals, we strive to uphold the high standards and reputation associated with this esteemed collection of publications.
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