Nuclear and mitochondrial genetic variants associated with mitochondrial DNA copy number

Koller A, Filosi M, Weissensteiner H, Fazzini F, Gorski M, Pattaro C, Schönherr S, Forer L, Herold JM, Stark KJ, Döttelmayer P, Hicks AA, Pramstaller PP, Würzner R, Eckardt KU, Heid IM, Fuchsberger C, Lamina C, Kronenberg F (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 14

Article Number: 2083

Journal Issue: 1

DOI: 10.1038/s41598-024-52373-0

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 × 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.

Authors with CRIS profile

Kai-Uwe Eckardt Department of Medicine 4 – Nephrology and Hypertension

Involved external institutions

Medizinische Universität Innsbruck AT Austria (AT) eurac research IT Italy (IT) Universität Regensburg DE Germany (DE)

How to cite

APA:

Koller, A., Filosi, M., Weissensteiner, H., Fazzini, F., Gorski, M., Pattaro, C.,... Kronenberg, F. (2024). Nuclear and mitochondrial genetic variants associated with mitochondrial DNA copy number. Scientific Reports, 14(1). https://dx.doi.org/10.1038/s41598-024-52373-0

MLA:

Koller, Adriana, et al. "Nuclear and mitochondrial genetic variants associated with mitochondrial DNA copy number." Scientific Reports 14.1 (2024).

BibTeX: Download