Koller, Adriana and Filosi, Michele and Weissensteiner, Hansi and Fazzini, Federica and Gorski, Mathias and Pattaro, Cristian and Schoenherr, Sebastian and Forer, Lukas and Herold, Janina M. and Stark, Klaus J. and Doettelmayer, Patricia and Hicks, Andrew A. and Pramstaller, Peter P. and Wuerzner, Reinhard and Eckardt, Kai-Uwe and Heid, Iris M. and Fuchsberger, Christian and Lamina, Claudia and Kronenberg, Florian (2024) Nuclear and mitochondrial genetic variants associated with mitochondrial DNA copy number. SCIENTIFIC REPORTS, 14 (1): 2083. ISSN 2045-2322
Full text not available from this repository. (Request a copy)Abstract
Mitochondrial DNA copy number (mtDNA-CN) is a biomarker for mitochondrial dysfunction associated with several diseases. Previous genome-wide association studies (GWAS) have been performed to unravel underlying mechanisms of mtDNA-CN regulation. However, the identified gene regions explain only a small fraction of mtDNA-CN variability. Most of this data has been estimated from microarrays based on various pipelines. In the present study we aimed to (1) identify genetic loci for qPCR-measured mtDNA-CN from three studies (16,130 participants) using GWAS, (2) identify potential systematic differences between our qPCR derived mtDNA-CN measurements compared to the published microarray intensity-based estimates, and (3) disentangle the nuclear from mitochondrial regulation of the mtDNA-CN phenotype. We identified two genome-wide significant autosomal loci associated with qPCR-measured mtDNA-CN: at HBS1L (rs4895440, p = 3.39 x 10-13) and GSDMA (rs56030650, p = 4.85 x 10-08) genes. Moreover, 113/115 of the previously published SNPs identified by microarray-based analyses were significantly equivalent with our findings. In our study, the mitochondrial genome itself contributed only marginally to mtDNA-CN regulation as we only detected a single rare mitochondrial variant associated with mtDNA-CN. Furthermore, we incorporated mitochondrial haplogroups into our analyses to explore their potential impact on mtDNA-CN. However, our findings indicate that they do not exert any significant influence on our results.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HBS1L-MYB INTERGENIC REGION; GENOME-WIDE ASSOCIATION; CALL FORMAT; METAANALYSIS; LOCI |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jan 2026 07:33 |
| Last Modified: | 15 Jan 2026 07:33 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65064 |
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