Mitochondrial DNA copy number in whole blood and glioma risk: A case control study

2016 ◽  
Vol 55 (12) ◽  
pp. 2089-2094 ◽  
Author(s):  
Jie Shen ◽  
Renduo Song ◽  
Zhimin Lu ◽  
Hua Zhao
Keyword(s):  
Mitochondrial Dna ◽  
Whole Blood ◽  
Copy Number ◽  
Case Control Study ◽  
Case Control ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
Glioma Risk ◽  
Control Study

scholarly journals A Case-Control Study of Peripheral Blood Mitochondrial DNA Copy Number and Risk of Renal Cell Carcinoma

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e43149 ◽  
Author(s):  
Mark P. Purdue ◽  
Jonathan N. Hofmann ◽  
Joanne S. Colt ◽  
Mirjam Hoxha ◽  
Julie J. Ruterbusch ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Mitochondrial Dna ◽  
Cell Carcinoma ◽  
Peripheral Blood ◽  
Renal Cell ◽  
Copy Number ◽  
Case Control Study ◽  
Case Control ◽  
Mitochondrial Dna Copy Number ◽  
Control Study

scholarly journals Mitochondrial DNA copy number and future risk of B-cell lymphoma in a nested case-control study in the prospective EPIC cohort

Blood ◽  
2014 ◽  
Vol 124 (4) ◽  
pp. 530-535 ◽  
Author(s):  
Fatemeh Saberi Hosnijeh ◽  
Qing Lan ◽  
Nathaniel Rothman ◽  
Chin San Liu ◽  
Wen-Ling Cheng ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
Key Points ◽  
Future Risk ◽  
Nested Case Control ◽  
Control Study

Key Points This study strengthens the previous observation of elevated mitochondrial DNA copy number and future risk of chronic lymphocytic leukemia.

scholarly journals Blood-derived mitochondrial DNA copy number is associated with gene expression across multiple tissues and is predictive for incident neurodegenerative disease

2020 ◽  
Author(s):  
Stephanie Y. Yang ◽  
Christina A. Castellani ◽  
Ryan J. Longchamps ◽  
Vamsee K. Pillalamarri ◽  
Brian O’Rourke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mitochondrial Dna ◽  
Neurodegenerative Disease ◽  
Whole Blood ◽  
Copy Number ◽  
Rna Binding ◽  
Inverse Association ◽  
Dna Copy Number ◽  
Related Disease ◽  
Mitochondrial Dna Copy Number

ABSTRACTBackgroundMitochondrial DNA copy number (mtDNA-CN) can be used as a proxy for mitochondrial function and is associated with a number of aging-related diseases. However, it is unclear how mtDNA-CN measured in blood can reflect risk for diseases that primarily manifest in other tissues. Using the Genotype-Tissue Expression Project, we interrogated the relationships between mtDNA-CN measured in whole blood and gene expression from whole blood as well as 47 additional tissues.ResultsWe evaluated associations between blood-derived mtDNA-CN and gene expression in whole blood for 418 individuals, correcting for known confounders and surrogate variables derived from RNA-sequencing. Using a permutation-derived cutoff (p<2.70e-6), mtDNA-CN was significantly associated with expression for 721 genes in whole blood, including nuclear genes that are required for mitochondrial DNA replication. Significantly enriched pathways included splicing (p=1.03e-8) and ubiquitin-mediated proteolysis (p=2.4e-10). Genes with target sequences for the mitochondrial transcription factor NRF1 were also enriched (p=1.76e-35).In non-blood tissues, there were more significantly associated genes than expected in 30 out of 47 tested tissues, suggesting that global gene expression in those tissues is correlated with mtDNA-CN. Pathways that were associated in multiple tissues included RNA-binding, catalysis, and neurodegenerative disease. We evaluated the association between mtDNA-CN and incident neurodegenerative disease in an independent dataset, the UK Biobank, using a Cox proportional-hazards model. Higher mtDNA-CN was significantly associated with lower risk for incident neurodegenerative disease (HR=0.73, 95% CI= 0.66;0.90).ConclusionsThe observation that mtDNA-CN measured in whole blood is associated with gene expression in other tissues suggests that blood-derived mtDNA-CN can reflect metabolic health across multiple tissues. Key pathways in maintaining cellular homeostasis, including splicing, RNA binding, and catalytic genes were significantly associated with mtDNA-CN, reinforcing the importance of mitochondria in aging-related disease. As a specific example, genes involved in neurodegenerative disease were significantly enriched in multiple tissues. This finding, validated in a large independent cohort study showing an inverse association between mtDNA-CN and neurodegenerative disease, solidifies the link between blood-derived mtDNA-CN, altered gene expression in both blood and non-blood tissues, and aging-related disease.

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