Understanding the function of regulatory DNA interactions in the interpretation of non-coding GWAS variants
Genome-wide association studies (GWAS) have identified a vast number of variants associated with various complex human diseases and traits. However, most of these GWAS variants reside in non-coding regions producing no proteins, making the interpretation of these variants a daunting challenge. Prior...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.957292/full |
| _version_ | 1811284031055069184 |
|---|---|
| author | Wujuan Zhong Weifang Liu Jiawen Chen Quan Sun Ming Hu Yun Li Yun Li Yun Li |
| author_facet | Wujuan Zhong Weifang Liu Jiawen Chen Quan Sun Ming Hu Yun Li Yun Li Yun Li |
| author_sort | Wujuan Zhong |
| collection | DOAJ |
| description | Genome-wide association studies (GWAS) have identified a vast number of variants associated with various complex human diseases and traits. However, most of these GWAS variants reside in non-coding regions producing no proteins, making the interpretation of these variants a daunting challenge. Prior evidence indicates that a subset of non-coding variants detected within or near cis-regulatory elements (e.g., promoters, enhancers, silencers, and insulators) might play a key role in disease etiology by regulating gene expression. Advanced sequencing- and imaging-based technologies, together with powerful computational methods, enabling comprehensive characterization of regulatory DNA interactions, have substantially improved our understanding of the three-dimensional (3D) genome architecture. Recent literature witnesses plenty of examples where using chromosome conformation capture (3C)-based technologies successfully links non-coding variants to their target genes and prioritizes relevant tissues or cell types. These examples illustrate the critical capability of 3D genome organization in annotating non-coding GWAS variants. This review discusses how 3D genome organization information contributes to elucidating the potential roles of non-coding GWAS variants in disease etiology. |
| first_indexed | 2024-04-13T02:22:32Z |
| format | Article |
| id | doaj.art-f0ddac51501b4fab9c223046d054fc1f |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-13T02:22:32Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-f0ddac51501b4fab9c223046d054fc1f2022-12-22T03:06:55ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-08-011010.3389/fcell.2022.957292957292Understanding the function of regulatory DNA interactions in the interpretation of non-coding GWAS variantsWujuan Zhong0Weifang Liu1Jiawen Chen2Quan Sun3Ming Hu4Yun Li5Yun Li6Yun Li7Biostatistics and Research Decision Sciences, Merck & Co, Inc, Rahway, NJ, United StatesDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, United StatesDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesGenome-wide association studies (GWAS) have identified a vast number of variants associated with various complex human diseases and traits. However, most of these GWAS variants reside in non-coding regions producing no proteins, making the interpretation of these variants a daunting challenge. Prior evidence indicates that a subset of non-coding variants detected within or near cis-regulatory elements (e.g., promoters, enhancers, silencers, and insulators) might play a key role in disease etiology by regulating gene expression. Advanced sequencing- and imaging-based technologies, together with powerful computational methods, enabling comprehensive characterization of regulatory DNA interactions, have substantially improved our understanding of the three-dimensional (3D) genome architecture. Recent literature witnesses plenty of examples where using chromosome conformation capture (3C)-based technologies successfully links non-coding variants to their target genes and prioritizes relevant tissues or cell types. These examples illustrate the critical capability of 3D genome organization in annotating non-coding GWAS variants. This review discusses how 3D genome organization information contributes to elucidating the potential roles of non-coding GWAS variants in disease etiology.https://www.frontiersin.org/articles/10.3389/fcell.2022.957292/full3D genome organizationGWAS variantsnon-coding DNA variationHi-CTADsFIREs |
| spellingShingle | Wujuan Zhong Weifang Liu Jiawen Chen Quan Sun Ming Hu Yun Li Yun Li Yun Li Understanding the function of regulatory DNA interactions in the interpretation of non-coding GWAS variants Frontiers in Cell and Developmental Biology 3D genome organization GWAS variants non-coding DNA variation Hi-C TADs FIREs |
| title | Understanding the function of regulatory DNA interactions in the interpretation of non-coding GWAS variants |
| title_full | Understanding the function of regulatory DNA interactions in the interpretation of non-coding GWAS variants |
| title_fullStr | Understanding the function of regulatory DNA interactions in the interpretation of non-coding GWAS variants |
| title_full_unstemmed | Understanding the function of regulatory DNA interactions in the interpretation of non-coding GWAS variants |
| title_short | Understanding the function of regulatory DNA interactions in the interpretation of non-coding GWAS variants |
| title_sort | understanding the function of regulatory dna interactions in the interpretation of non coding gwas variants |
| topic | 3D genome organization GWAS variants non-coding DNA variation Hi-C TADs FIREs |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.957292/full |
| work_keys_str_mv | AT wujuanzhong understandingthefunctionofregulatorydnainteractionsintheinterpretationofnoncodinggwasvariants AT weifangliu understandingthefunctionofregulatorydnainteractionsintheinterpretationofnoncodinggwasvariants AT jiawenchen understandingthefunctionofregulatorydnainteractionsintheinterpretationofnoncodinggwasvariants AT quansun understandingthefunctionofregulatorydnainteractionsintheinterpretationofnoncodinggwasvariants AT minghu understandingthefunctionofregulatorydnainteractionsintheinterpretationofnoncodinggwasvariants AT yunli understandingthefunctionofregulatorydnainteractionsintheinterpretationofnoncodinggwasvariants AT yunli understandingthefunctionofregulatorydnainteractionsintheinterpretationofnoncodinggwasvariants AT yunli understandingthefunctionofregulatorydnainteractionsintheinterpretationofnoncodinggwasvariants |