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Koller, Adriana; Filosi, Michele; Weissensteiner, Hansi; Fazzini, Federica; Gorski, Mathias; Pattaro, Cristian; Schönherr, Sebastian; Forer, Lukas; Herold, Janina M.; Stark, Klaus J.; Döttelmayer, Patricia; Hicks, Andrew A.; Pramstaller, Peter P.; Würzner, Reinhard; Eckardt, Kai-Uwe; Heid, Iris M.; Fuchsberger, Christian; Lamina, Claudia; Kronenberg, Florian

Nuclear and mitochondrial genetic variants associated with mitochondrial DNA copy number

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  • Media type: E-Article
  • Title: Nuclear and mitochondrial genetic variants associated with mitochondrial DNA copy number
  • Contributor: Koller, Adriana; Filosi, Michele; Weissensteiner, Hansi; Fazzini, Federica; Gorski, Mathias; Pattaro, Cristian; Schönherr, Sebastian; Forer, Lukas; Herold, Janina M.; Stark, Klaus J.; Döttelmayer, Patricia; Hicks, Andrew A.; Pramstaller, Peter P.; Würzner, Reinhard; Eckardt, Kai-Uwe; Heid, Iris M.; Fuchsberger, Christian; Lamina, Claudia; Kronenberg, Florian
  • Published: Springer Science and Business Media LLC, 2024
  • Published in: Scientific Reports, 14 (2024) 1
  • Language: English
  • DOI: 10.1038/s41598-024-52373-0
  • ISSN: 2045-2322
  • Origination:
  • Footnote:
  • Description: AbstractMitochondrial 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 × 10–13) and GSDMA (rs56030650, p = 4.85 × 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.
  • Access State: Open Access