NHLBI CHARGE-S
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA242325 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Building on GWAS for NHLBI-diseases: the U.S. CHARGE consortium (CHARGE-S): ARIC
| PRJNA222877 | ENA
Project description:Building on GWAS for NHLBI-diseases: the U.S. CHARGE consortium (CHARGE-S): CHS
| PRJNA226743 | ENA
Project description:Building on GWAS for NHLBI-diseases: the U.S. CHARGE consortium (CHARGE-S): Framingham Heart Study
| PRJNA215134 | ENA
Project description:Building on GWAS for NHLBI-diseases: the U.S. CHARGE consortium (CHARGE-S): MGH AF Study
| PRJNA354108 | ENA
Project description:NHLBI TOPMed: Cardiovascular Health Study (CHS)
| PRJNA385053 | ENA
Project description:NHLBI GO-ESP: Heart Cohorts Exome Sequencing Project (ARIC)
| PRJNA75755 | ENA
Project description:NHLBI GO-ESP: Heart Cohorts Exome Sequencing Project (CHS)
| PRJNA75759 | ENA
Project description:Mitochondrial DNA copy number (mtDNA-CN) has been associated with a variety of aging-related diseases, including all-cause mortality. However, the mechanism by which mtDNA-CN influences disease is not currently understood. One such mechanism may be through regulation of nuclear gene expression via the modification of nuclear DNA (nDNA) methylation. To investigate this hypothesis, we assessed the relationship between mtDNA-CN and nDNA methylation in 2,507 African American (AA) and European Americans (EA) participants from the Atherosclerosis Risk in Communities (ARIC) study using the Infinium Human Methylation 450K Beadchip (485,764 CpGs). Thirty-four independent CpGs were associated with mtDNA-CN at genome-wide significance (P<5x10-8). To validate our findings we assayed an additional 2,528 participants from the Cardiovascular Health Study (CHS) (N=533) and Framingham Heart Study (FHS) (N=1995). Meta-analysis across all cohorts identified 6 mtDNA-CN associated CpGs to be validated ac ross cohorts at genome-wide significance (P<5x10-8). Additionally, over half of these CpGs were associated with phenotypes known to be associated with mtDNA-CN, including CHD, CVD, and mortality. Experimental modification of mtDNA-CN through knockout via CRISPR-Cas9 of TFAM, a regulator of mtDNA replication, demonstrated that modulation of mtDNA-CN directly drives changes in nDNA methylation and gene expression of specific CpGs and nearby transcripts. Strikingly, the ‘neuroactive ligand receptor interaction’ KEGG pathway was found to be highly overrepresented in the ARIC cohort (P= 5.24x10-12), as well as the TFAM knockout methylation (P=4.41x10-4) and expression (P=4.30x10-4) studies. These results demonstrate that changes in mtDNA-CN influence nDNA methylation at specific loci and result in differential gene expression of specific genes, including those acting in the ‘neuroactive ligand receptor interaction’ pathway that may impact human health and disease via altered cell signaling.
2019-07-09 | GSE133994 | GEO
Project description:HEK293 cells with CRISPR KO were analyzed using RNA-Seq. Abstract: Mitochondrial DNA copy number (mtDNA-CN) has been associated with a variety of aging-related diseases, including all-cause mortality. However, the mechanism by which mtDNA-CN influences disease is not currently understood. One such mechanism may be through regulation of nuclear gene expression via the modification of nuclear DNA (nDNA) methylation. To investigate this hypothesis, we assessed the relationship between mtDNA-CN and nDNA methylation in 2,507 African American (AA) and European Americans (EA) participants from the Atherosclerosis Risk in Communities (ARIC) study using the Infinium Human Methylation 450K Beadchip (485,764 CpGs). Thirty-four independent CpGs were associated with mtDNA-CN at genome-wide significance (P<5x10-8). To validate our findings we assayed an additional 2,528 participants from the Cardiovascular Health Study (CHS) (N=533) and Framingham Heart Study (FHS) (N=1995). Meta-analysis across all cohorts identified 6 mtDNA-CN associated CpGs to be validated across cohorts at genome-wide significance (P<5x10-8). Additionally, over half of these CpGs were associated with phenotypes known to be associated with mtDNA-CN, including CHD, CVD, and mortality. Experimental modification of mtDNA-CN through knockout via CRISPR-Cas9 of TFAM, a regulator of mtDNA replication, demonstrated that modulation of mtDNA-CN directly drives changes in nDNA methylation and gene expression of specific CpGs and nearby transcripts. Strikingly, the ‘neuroactive ligand receptor interaction’ KEGG pathway was found to be highly overrepresented in the ARIC cohort (P= 5.24x10-12), as well as the TFAM knockout methylation (P=4.41x10-4) and expression (P=4.30x10-4) studies. These results demonstrate that changes in mtDNA-CN influence nDNA methylation at specific loci and result in differential gene expression of specific genes, including those acting in the ‘neuroactive ligand receptor interaction’ pathway that may impact human health and disease via altered cell signaling.
2019-07-10 | GSE134048 | GEO