Dynamic effects of genetic variation on gene expression revealed following hypoxic stress in cardiomyocytes
© 2021, Ward et al..
One life-threatening outcome of cardiovascular disease is myocardial infarction, where cardiomyocytes are deprived of oxygen. To study inter-individual differences in response to hypoxia, we established an in vitro model of induced pluripotent stem cell-derived cardiomyocytes from 15 individuals. We measured gene expression levels, chromatin accessibility, and methylation levels in four culturing conditions that correspond to normoxia, hypoxia, and short- or long-term re-oxygenation. We characterized thousands of gene regulatory changes as the cells transition between conditions. Using available genotypes, we identified 1,573 genes with a cis expression quantitative locus (eQTL) in at least one condition, as well as 367 dynamic eQTLs, which are classified as eQTLs in at least one, but not in all conditions. A subset of genes with dynamic eQTLs is associated with complex traits and disease. Our data demonstrate how dynamic genetic effects on gene expression, which are likely relevant for disease, can be uncovered under stress.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
eLife - 10(2021) vom: 08. Feb. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ward, Michelle C [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 08.02.2022 Date Revised 08.02.2022 published: Electronic GEO: GSE144426 Citation Status MEDLINE |
|---|
| doi: |
10.7554/eLife.57345 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM32115374X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM32115374X | ||
| 003 | DE-627 | ||
| 005 | 20231225175215.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.7554/eLife.57345 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1070.xml |
| 035 | |a (DE-627)NLM32115374X | ||
| 035 | |a (NLM)33554857 | ||
| 035 | |a (PII)e57345 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ward, Michelle C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dynamic effects of genetic variation on gene expression revealed following hypoxic stress in cardiomyocytes |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.02.2022 | ||
| 500 | |a Date Revised 08.02.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a GEO: GSE144426 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021, Ward et al. | ||
| 520 | |a One life-threatening outcome of cardiovascular disease is myocardial infarction, where cardiomyocytes are deprived of oxygen. To study inter-individual differences in response to hypoxia, we established an in vitro model of induced pluripotent stem cell-derived cardiomyocytes from 15 individuals. We measured gene expression levels, chromatin accessibility, and methylation levels in four culturing conditions that correspond to normoxia, hypoxia, and short- or long-term re-oxygenation. We characterized thousands of gene regulatory changes as the cells transition between conditions. Using available genotypes, we identified 1,573 genes with a cis expression quantitative locus (eQTL) in at least one condition, as well as 367 dynamic eQTLs, which are classified as eQTLs in at least one, but not in all conditions. A subset of genes with dynamic eQTLs is associated with complex traits and disease. Our data demonstrate how dynamic genetic effects on gene expression, which are likely relevant for disease, can be uncovered under stress | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a cardiomyocytes | |
| 650 | 4 | |a chromosomes | |
| 650 | 4 | |a eQTL | |
| 650 | 4 | |a gene expression | |
| 650 | 4 | |a gene regulation | |
| 650 | 4 | |a genetic variation | |
| 650 | 4 | |a genetics | |
| 650 | 4 | |a genomics | |
| 650 | 4 | |a human | |
| 650 | 4 | |a hypoxia | |
| 650 | 4 | |a stress response | |
| 650 | 7 | |a Oxygen |2 NLM | |
| 650 | 7 | |a S88TT14065 |2 NLM | |
| 700 | 1 | |a Banovich, Nicholas E |e verfasserin |4 aut | |
| 700 | 1 | |a Sarkar, Abhishek |e verfasserin |4 aut | |
| 700 | 1 | |a Stephens, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Gilad, Yoav |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t eLife |d 2012 |g 10(2021) vom: 08. Feb. |w (DE-627)NLM221831460 |x 2050-084X |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2021 |g day:08 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.7554/eLife.57345 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2021 |b 08 |c 02 | ||