tetano
Editor, Senior Moderator
Nat Genet
. 2024 Feb 29.
doi: 10.1038/s41588-024-01668-z. Online ahead of print. Epigenetic variation impacts individual differences in the transcriptional response to influenza infection
Katherine A Aracena[SUP] 1 [/SUP], Yen-Lung Lin[SUP] 2 [/SUP], Kaixuan Luo[SUP] 1 [/SUP], Alain Pacis[SUP] 3 [/SUP], Saideep Gona[SUP] 2 [/SUP], Zepeng Mu[SUP] 1 [/SUP], Vania Yotova[SUP] 4 [/SUP], Renata Sindeaux[SUP] 4 [/SUP], Albena Pramatarova[SUP] 5 [/SUP], Marie-Michelle Simon[SUP] 5 [/SUP], Xun Chen[SUP] 6 [/SUP], Cristian Groza[SUP] 7 [/SUP], David Lougheed[SUP] 3 8 [/SUP], Romain Gregoire[SUP] 3 [/SUP], David Brownlee[SUP] 3 [/SUP], Carly Boye[SUP] 9 [/SUP], Roger Pique-Regi[SUP] 9 10 [/SUP], Yang Li[SUP] 1 [/SUP], Xin He[SUP] 1 [/SUP], David Bujold[SUP] 3 5 [/SUP], Tomi Pastinen[SUP] 8 11 [/SUP], Guillaume Bourque[SUP] 12 13 14 15 [/SUP], Luis B Barreiro[SUP] 16 17 18 [/SUP]
Affiliations
Humans display remarkable interindividual variation in their immune response to identical challenges. Yet, our understanding of the genetic and epigenetic factors contributing to such variation remains limited. Here we performed in-depth genetic, epigenetic and transcriptional profiling on primary macrophages derived from individuals of European and African ancestry before and after infection with influenza A virus. We show that baseline epigenetic profiles are strongly predictive of the transcriptional response to influenza A virus across individuals. Quantitative trait locus (QTL) mapping revealed highly coordinated genetic effects on gene regulation, with many cis-acting genetic variants impacting concomitantly gene expression and multiple epigenetic marks. These data reveal that ancestry-associated differences in the epigenetic landscape can be genetically controlled, even more than gene expression. Lastly, among QTL variants that colocalized with immune-disease loci, only 7% were gene expression QTL, while the remaining genetic variants impact epigenetic marks, stressing the importance of considering molecular phenotypes beyond gene expression in disease-focused studies.
. 2024 Feb 29.
doi: 10.1038/s41588-024-01668-z. Online ahead of print. Epigenetic variation impacts individual differences in the transcriptional response to influenza infection
Katherine A Aracena[SUP] 1 [/SUP], Yen-Lung Lin[SUP] 2 [/SUP], Kaixuan Luo[SUP] 1 [/SUP], Alain Pacis[SUP] 3 [/SUP], Saideep Gona[SUP] 2 [/SUP], Zepeng Mu[SUP] 1 [/SUP], Vania Yotova[SUP] 4 [/SUP], Renata Sindeaux[SUP] 4 [/SUP], Albena Pramatarova[SUP] 5 [/SUP], Marie-Michelle Simon[SUP] 5 [/SUP], Xun Chen[SUP] 6 [/SUP], Cristian Groza[SUP] 7 [/SUP], David Lougheed[SUP] 3 8 [/SUP], Romain Gregoire[SUP] 3 [/SUP], David Brownlee[SUP] 3 [/SUP], Carly Boye[SUP] 9 [/SUP], Roger Pique-Regi[SUP] 9 10 [/SUP], Yang Li[SUP] 1 [/SUP], Xin He[SUP] 1 [/SUP], David Bujold[SUP] 3 5 [/SUP], Tomi Pastinen[SUP] 8 11 [/SUP], Guillaume Bourque[SUP] 12 13 14 15 [/SUP], Luis B Barreiro[SUP] 16 17 18 [/SUP]
Affiliations
- PMID: 38424460
- DOI: 10.1038/s41588-024-01668-z
Humans display remarkable interindividual variation in their immune response to identical challenges. Yet, our understanding of the genetic and epigenetic factors contributing to such variation remains limited. Here we performed in-depth genetic, epigenetic and transcriptional profiling on primary macrophages derived from individuals of European and African ancestry before and after infection with influenza A virus. We show that baseline epigenetic profiles are strongly predictive of the transcriptional response to influenza A virus across individuals. Quantitative trait locus (QTL) mapping revealed highly coordinated genetic effects on gene regulation, with many cis-acting genetic variants impacting concomitantly gene expression and multiple epigenetic marks. These data reveal that ancestry-associated differences in the epigenetic landscape can be genetically controlled, even more than gene expression. Lastly, among QTL variants that colocalized with immune-disease loci, only 7% were gene expression QTL, while the remaining genetic variants impact epigenetic marks, stressing the importance of considering molecular phenotypes beyond gene expression in disease-focused studies.