Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex Diseases
Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleoti...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BioMed Central
2014-12-01
|
| Series: | Genomics & Informatics |
| Subjects: | |
| Online Access: | http://genominfo.org/upload/pdf/gni-12-181.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832573261668417536 |
|---|---|
| author | Min Kyung Sung Hyoeun Bang Jung Kyoon Choi |
| author_facet | Min Kyung Sung Hyoeun Bang Jung Kyoon Choi |
| author_sort | Min Kyung Sung |
| collection | DOAJ |
| description | Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleotide polymorphisms resides in non-coding regions, making it difficult to understand their phenotypic contribution. In this work, we studied epistatic interactions associated with three common diseases using Korea Association Resource (KARE) data: type 2 diabetes mellitus (DM), hypertension (HT), and coronary artery disease (CAD). We showed that epistatic single-nucleotide polymorphisms (SNPs) were enriched in enhancers, as well as in DNase I footprints (the Encyclopedia of DNA Elements [ENCODE] Project Consortium 2012), which suggested that the disruption of the regulatory regions where transcription factors bind may be involved in the disease mechanism. Accordingly, to identify the genes affected by the SNPs, we employed whole-genome multiple-cell-type enhancer data which discovered using DNase I profiles and Cap Analysis Gene Expression (CAGE). Assigned genes were significantly enriched in known disease associated gene sets, which were explored based on the literature, suggesting that this approach is useful for detecting relevant affected genes. In our knowledge-based epistatic network, the three diseases share many associated genes and are also closely related with each other through many epistatic interactions. These findings elucidate the genetic basis of the close relationship between DM, HT, and CAD. |
| format | Article |
| id | doaj-art-02c5b7cc89b749d592fd54221b6fba80 |
| institution | Kabale University |
| issn | 1598-866X 2234-0742 |
| language | English |
| publishDate | 2014-12-01 |
| publisher | BioMed Central |
| record_format | Article |
| series | Genomics & Informatics |
| spelling | doaj-art-02c5b7cc89b749d592fd54221b6fba802025-02-02T05:17:10ZengBioMed CentralGenomics & Informatics1598-866X2234-07422014-12-0112418118610.5808/GI.2014.12.4.181104Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex DiseasesMin Kyung Sung0Hyoeun Bang1Jung Kyoon Choi2Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleotide polymorphisms resides in non-coding regions, making it difficult to understand their phenotypic contribution. In this work, we studied epistatic interactions associated with three common diseases using Korea Association Resource (KARE) data: type 2 diabetes mellitus (DM), hypertension (HT), and coronary artery disease (CAD). We showed that epistatic single-nucleotide polymorphisms (SNPs) were enriched in enhancers, as well as in DNase I footprints (the Encyclopedia of DNA Elements [ENCODE] Project Consortium 2012), which suggested that the disruption of the regulatory regions where transcription factors bind may be involved in the disease mechanism. Accordingly, to identify the genes affected by the SNPs, we employed whole-genome multiple-cell-type enhancer data which discovered using DNase I profiles and Cap Analysis Gene Expression (CAGE). Assigned genes were significantly enriched in known disease associated gene sets, which were explored based on the literature, suggesting that this approach is useful for detecting relevant affected genes. In our knowledge-based epistatic network, the three diseases share many associated genes and are also closely related with each other through many epistatic interactions. These findings elucidate the genetic basis of the close relationship between DM, HT, and CAD.http://genominfo.org/upload/pdf/gni-12-181.pdfcoronary artery diseasediabetes mellitusepistasishypertensionregulatory region |
| spellingShingle | Min Kyung Sung Hyoeun Bang Jung Kyoon Choi Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex Diseases Genomics & Informatics coronary artery disease diabetes mellitus epistasis hypertension regulatory region |
| title | Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex Diseases |
| title_full | Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex Diseases |
| title_fullStr | Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex Diseases |
| title_full_unstemmed | Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex Diseases |
| title_short | Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex Diseases |
| title_sort | understanding epistatic interactions between genes targeted by non coding regulatory elements in complex diseases |
| topic | coronary artery disease diabetes mellitus epistasis hypertension regulatory region |
| url | http://genominfo.org/upload/pdf/gni-12-181.pdf |
| work_keys_str_mv | AT minkyungsung understandingepistaticinteractionsbetweengenestargetedbynoncodingregulatoryelementsincomplexdiseases AT hyoeunbang understandingepistaticinteractionsbetweengenestargetedbynoncodingregulatoryelementsincomplexdiseases AT jungkyoonchoi understandingepistaticinteractionsbetweengenestargetedbynoncodingregulatoryelementsincomplexdiseases |