Gjoneska E, Pfenning AR, Mathys H, Quon G, Kundaje A, Tsai LH, Kellis M.
Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer's disease.
Nature. 2015 Feb 19;518(7539):365-9.
PubMed.
The Roadmap Epigenomics Consortium has set out an essential resource for researchers studying the epigenome. There are a number of key findings, among which are that epigenomic data sets can be imputed at high resolution and that disease-associated genetic variants show epigenomic enrichments in tissues relevant to the disease. This also means that where enrichment is seen in a tissue, it can be regarded as important for that disease. For Alzheimer’s, researchers find that immune cells show a signal consistent with the genetic evidence that the immune response plays a part in Alzheimer’s disease. An interesting aspect of this finding is that regions of the genome that do not quite reach genome-wide significance in GWAS are implicated by epigenomics, providing additional support for their involvement. In other words, the genomic and epigenomic evidence support each other.
Epigenetics is an exciting and developing field. These papers represent an excellent first step to allow researchers to unravel the epigenetic architecture of diseases such as Alzheimer’s. The epigenomic roadmap provides a platform to advance our understanding of the genetic associations and biological pathways identified as important in disease etiology. The work on animal models further supports the primary role of immunity in disease, which has been highlighted by the function of a number of the AD susceptibility genes, and pathway analyses of genome-wide association datasets. It will be of great interest to the Alzheimer’s field to see how these findings from animal models translate into human studies.
The wealth of data laid out by the Roadmap Epigenomics Consortium is both exciting and overwhelming. By adding together several layers of data, including multiple measures of DNA methylation, histone methylation marks, DNaseI digestion, and RNA sequencing, we can begin to build a more complete picture of how gene transcription is regulated in various cell types. Comparing pluripotent, multipotent, and fully differentiated cells gives us a glimpse into how epigenetics plays a role in lineage specification and helps us determine which genes are vital for this process.
Environmental contributions to complex diseases like Alzheimer’s have always been hard to define. We are now beginning to understand how things such as diet and exercise can influence gene transcription by altering their epigenetic regulation. The data presented by the Consortium will help us narrow our focus in this regard. By defining transcriptionally active/repressed genes in the brain and understanding the epigenetic signature responsible for that state, we can start selecting candidate genes whose transcription could be altered by the environment. The caveat is that people are not a homogeneous population of lab animals. Our challenge for the future will be to determine how variable these epigenetic signatures are across populations.
Comments
Kings College London
The Roadmap Epigenomics Consortium has set out an essential resource for researchers studying the epigenome. There are a number of key findings, among which are that epigenomic data sets can be imputed at high resolution and that disease-associated genetic variants show epigenomic enrichments in tissues relevant to the disease. This also means that where enrichment is seen in a tissue, it can be regarded as important for that disease. For Alzheimer’s, researchers find that immune cells show a signal consistent with the genetic evidence that the immune response plays a part in Alzheimer’s disease. An interesting aspect of this finding is that regions of the genome that do not quite reach genome-wide significance in GWAS are implicated by epigenomics, providing additional support for their involvement. In other words, the genomic and epigenomic evidence support each other.
Cardiff University
Epigenetics is an exciting and developing field. These papers represent an excellent first step to allow researchers to unravel the epigenetic architecture of diseases such as Alzheimer’s. The epigenomic roadmap provides a platform to advance our understanding of the genetic associations and biological pathways identified as important in disease etiology. The work on animal models further supports the primary role of immunity in disease, which has been highlighted by the function of a number of the AD susceptibility genes, and pathway analyses of genome-wide association datasets. It will be of great interest to the Alzheimer’s field to see how these findings from animal models translate into human studies.
View all comments by Rebecca SimsUniversity of Toronto
The wealth of data laid out by the Roadmap Epigenomics Consortium is both exciting and overwhelming. By adding together several layers of data, including multiple measures of DNA methylation, histone methylation marks, DNaseI digestion, and RNA sequencing, we can begin to build a more complete picture of how gene transcription is regulated in various cell types. Comparing pluripotent, multipotent, and fully differentiated cells gives us a glimpse into how epigenetics plays a role in lineage specification and helps us determine which genes are vital for this process.
Environmental contributions to complex diseases like Alzheimer’s have always been hard to define. We are now beginning to understand how things such as diet and exercise can influence gene transcription by altering their epigenetic regulation. The data presented by the Consortium will help us narrow our focus in this regard. By defining transcriptionally active/repressed genes in the brain and understanding the epigenetic signature responsible for that state, we can start selecting candidate genes whose transcription could be altered by the environment. The caveat is that people are not a homogeneous population of lab animals. Our challenge for the future will be to determine how variable these epigenetic signatures are across populations.
View all comments by Erin KnockMake a Comment
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