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Unique roles of rare variants in the genetics of complex diseases in humans

Genome-wide association studies have identified >10,000 genetic variants associated with various phenotypes and diseases. Although the majority are common variants, rare variants with >0.1% of minor allele frequency have been investigated by imputation and using disease-specific custom SNP arr...

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Autores principales: Momozawa, Yukihide, Mizukami, Keijiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728599/
https://www.ncbi.nlm.nih.gov/pubmed/32948841
http://dx.doi.org/10.1038/s10038-020-00845-2
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author Momozawa, Yukihide
Mizukami, Keijiro
author_facet Momozawa, Yukihide
Mizukami, Keijiro
author_sort Momozawa, Yukihide
collection PubMed
description Genome-wide association studies have identified >10,000 genetic variants associated with various phenotypes and diseases. Although the majority are common variants, rare variants with >0.1% of minor allele frequency have been investigated by imputation and using disease-specific custom SNP arrays. Rare variants sequencing analysis mainly revealed have played unique roles in the genetics of complex diseases in humans due to their distinctive features, in contrast to common variants. Unique roles are hypothesis-free evidence for gene causality, a precise target of functional analysis for understanding disease mechanisms, a new favorable target for drug development, and a genetic marker with high disease risk for personalized medicine. As whole-genome sequencing continues to identify more rare variants, the roles associated with rare variants will also increase. However, a better estimation of the functional impact of rare variants across whole genome is needed to enhance their contribution to improvements in human health.
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spelling pubmed-77285992020-12-17 Unique roles of rare variants in the genetics of complex diseases in humans Momozawa, Yukihide Mizukami, Keijiro J Hum Genet Review Article Genome-wide association studies have identified >10,000 genetic variants associated with various phenotypes and diseases. Although the majority are common variants, rare variants with >0.1% of minor allele frequency have been investigated by imputation and using disease-specific custom SNP arrays. Rare variants sequencing analysis mainly revealed have played unique roles in the genetics of complex diseases in humans due to their distinctive features, in contrast to common variants. Unique roles are hypothesis-free evidence for gene causality, a precise target of functional analysis for understanding disease mechanisms, a new favorable target for drug development, and a genetic marker with high disease risk for personalized medicine. As whole-genome sequencing continues to identify more rare variants, the roles associated with rare variants will also increase. However, a better estimation of the functional impact of rare variants across whole genome is needed to enhance their contribution to improvements in human health. Springer Singapore 2020-09-18 2021 /pmc/articles/PMC7728599/ /pubmed/32948841 http://dx.doi.org/10.1038/s10038-020-00845-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Review Article
Momozawa, Yukihide
Mizukami, Keijiro
Unique roles of rare variants in the genetics of complex diseases in humans
title Unique roles of rare variants in the genetics of complex diseases in humans
title_full Unique roles of rare variants in the genetics of complex diseases in humans
title_fullStr Unique roles of rare variants in the genetics of complex diseases in humans
title_full_unstemmed Unique roles of rare variants in the genetics of complex diseases in humans
title_short Unique roles of rare variants in the genetics of complex diseases in humans
title_sort unique roles of rare variants in the genetics of complex diseases in humans
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728599/
https://www.ncbi.nlm.nih.gov/pubmed/32948841
http://dx.doi.org/10.1038/s10038-020-00845-2
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