Interactions between genetic variation and cellular environment in skeletal muscle gene expression.
From whole organisms to individual cells, responses to environmental conditions are influenced by genetic makeup, where the effect of genetic variation on a trait depends on the environmental context. RNA-sequencing quantifies gene expression as a molecular trait, and is capable of capturing both ge...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0195788 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849428050403393536 |
|---|---|
| author | D Leland Taylor David A Knowles Laura J Scott Andrea H Ramirez Francesco Paolo Casale Brooke N Wolford Li Guan Arushi Varshney Ricardo D'Oliveira Albanus Stephen C J Parker Narisu Narisu Peter S Chines Michael R Erdos Ryan P Welch Leena Kinnunen Jouko Saramies Jouko Sundvall Timo A Lakka Markku Laakso Jaakko Tuomilehto Heikki A Koistinen Oliver Stegle Michael Boehnke Ewan Birney Francis S Collins |
| author_facet | D Leland Taylor David A Knowles Laura J Scott Andrea H Ramirez Francesco Paolo Casale Brooke N Wolford Li Guan Arushi Varshney Ricardo D'Oliveira Albanus Stephen C J Parker Narisu Narisu Peter S Chines Michael R Erdos Ryan P Welch Leena Kinnunen Jouko Saramies Jouko Sundvall Timo A Lakka Markku Laakso Jaakko Tuomilehto Heikki A Koistinen Oliver Stegle Michael Boehnke Ewan Birney Francis S Collins |
| author_sort | D Leland Taylor |
| collection | DOAJ |
| description | From whole organisms to individual cells, responses to environmental conditions are influenced by genetic makeup, where the effect of genetic variation on a trait depends on the environmental context. RNA-sequencing quantifies gene expression as a molecular trait, and is capable of capturing both genetic and environmental effects. In this study, we explore opportunities of using allele-specific expression (ASE) to discover cis-acting genotype-environment interactions (GxE)-genetic effects on gene expression that depend on an environmental condition. Treating 17 common, clinical traits as approximations of the cellular environment of 267 skeletal muscle biopsies, we identify 10 candidate environmental response expression quantitative trait loci (reQTLs) across 6 traits (12 unique gene-environment trait pairs; 10% FDR per trait) including sex, systolic blood pressure, and low-density lipoprotein cholesterol. Although using ASE is in principle a promising approach to detect GxE effects, replication of such signals can be challenging as validation requires harmonization of environmental traits across cohorts and a sufficient sampling of heterozygotes for a transcribed SNP. Comprehensive discovery and replication will require large human transcriptome datasets, or the integration of multiple transcribed SNPs, coupled with standardized clinical phenotyping. |
| format | Article |
| id | doaj-art-0de5691bc69c48a5a92bbc0b581ecb65 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-0de5691bc69c48a5a92bbc0b581ecb652025-08-20T03:28:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01134e019578810.1371/journal.pone.0195788Interactions between genetic variation and cellular environment in skeletal muscle gene expression.D Leland TaylorDavid A KnowlesLaura J ScottAndrea H RamirezFrancesco Paolo CasaleBrooke N WolfordLi GuanArushi VarshneyRicardo D'Oliveira AlbanusStephen C J ParkerNarisu NarisuPeter S ChinesMichael R ErdosRyan P WelchLeena KinnunenJouko SaramiesJouko SundvallTimo A LakkaMarkku LaaksoJaakko TuomilehtoHeikki A KoistinenOliver StegleMichael BoehnkeEwan BirneyFrancis S CollinsFrom whole organisms to individual cells, responses to environmental conditions are influenced by genetic makeup, where the effect of genetic variation on a trait depends on the environmental context. RNA-sequencing quantifies gene expression as a molecular trait, and is capable of capturing both genetic and environmental effects. In this study, we explore opportunities of using allele-specific expression (ASE) to discover cis-acting genotype-environment interactions (GxE)-genetic effects on gene expression that depend on an environmental condition. Treating 17 common, clinical traits as approximations of the cellular environment of 267 skeletal muscle biopsies, we identify 10 candidate environmental response expression quantitative trait loci (reQTLs) across 6 traits (12 unique gene-environment trait pairs; 10% FDR per trait) including sex, systolic blood pressure, and low-density lipoprotein cholesterol. Although using ASE is in principle a promising approach to detect GxE effects, replication of such signals can be challenging as validation requires harmonization of environmental traits across cohorts and a sufficient sampling of heterozygotes for a transcribed SNP. Comprehensive discovery and replication will require large human transcriptome datasets, or the integration of multiple transcribed SNPs, coupled with standardized clinical phenotyping.https://doi.org/10.1371/journal.pone.0195788 |
| spellingShingle | D Leland Taylor David A Knowles Laura J Scott Andrea H Ramirez Francesco Paolo Casale Brooke N Wolford Li Guan Arushi Varshney Ricardo D'Oliveira Albanus Stephen C J Parker Narisu Narisu Peter S Chines Michael R Erdos Ryan P Welch Leena Kinnunen Jouko Saramies Jouko Sundvall Timo A Lakka Markku Laakso Jaakko Tuomilehto Heikki A Koistinen Oliver Stegle Michael Boehnke Ewan Birney Francis S Collins Interactions between genetic variation and cellular environment in skeletal muscle gene expression. PLoS ONE |
| title | Interactions between genetic variation and cellular environment in skeletal muscle gene expression. |
| title_full | Interactions between genetic variation and cellular environment in skeletal muscle gene expression. |
| title_fullStr | Interactions between genetic variation and cellular environment in skeletal muscle gene expression. |
| title_full_unstemmed | Interactions between genetic variation and cellular environment in skeletal muscle gene expression. |
| title_short | Interactions between genetic variation and cellular environment in skeletal muscle gene expression. |
| title_sort | interactions between genetic variation and cellular environment in skeletal muscle gene expression |
| url | https://doi.org/10.1371/journal.pone.0195788 |
| work_keys_str_mv | AT dlelandtaylor interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT davidaknowles interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT laurajscott interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT andreahramirez interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT francescopaolocasale interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT brookenwolford interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT liguan interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT arushivarshney interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT ricardodoliveiraalbanus interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT stephencjparker interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT narisunarisu interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT peterschines interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT michaelrerdos interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT ryanpwelch interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT leenakinnunen interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT joukosaramies interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT joukosundvall interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT timoalakka interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT markkulaakso interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT jaakkotuomilehto interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT heikkiakoistinen interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT oliverstegle interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT michaelboehnke interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT ewanbirney interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression AT francisscollins interactionsbetweengeneticvariationandcellularenvironmentinskeletalmusclegeneexpression |