Genome-wide association study of mitochondrial copy number
Mitochondrial DNA copy number (mtDNAcn) variation has been associated with increased risk of several human diseases in epidemiological studies. The quantification of mtDNAcn performed with real-time PCR is currently considered the de facto standard among several techniques. However, the heterogeneit...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2022
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| In: |
Human molecular genetics
Year: 2022, Volume: 31, Issue: 8, Pages: 1346-1355 |
| ISSN: | 1460-2083 |
| DOI: | 10.1093/hmg/ddab341 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/hmg/ddab341
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| Author Notes: | Manuel Gentiluomo, Matteo Giaccherini, Xīn Gào, Feng Guo, Hannah Stocker, Ben Schöttker, Hermann Brenner, Federico Canzian and Daniele Campa |
| Summary: | Mitochondrial DNA copy number (mtDNAcn) variation has been associated with increased risk of several human diseases in epidemiological studies. The quantification of mtDNAcn performed with real-time PCR is currently considered the de facto standard among several techniques. However, the heterogeneity of the laboratory methods (DNA extraction, storage, processing) used could give rise to results that are difficult to compare and reproduce across different studies. Several lines of evidence suggest that mtDNAcn is influenced by nuclear and mitochondrial genetic variability, however this relation is largely unexplored. The aim of this work was to elucidate the genetic basis of mtDNAcn variation. We performed a genome-wide association study (GWAS) of mtDNAcn in 6836 subjects from the ESTHER prospective cohort, and included, as replication set, the summary statistics of a GWAS that used 295 150 participants from the UK Biobank. We observed two novel associations with mtDNAcn variation on chromosome 19 (rs117176661), and 12 (rs7136238) that reached statistical significance at the genome-wide level. A polygenic score that we called mitoscore including all known single nucleotide polymorphisms explained 1.11% of the variation of mtDNAcn (p = 5.93 × 10−7). In conclusion, we performed a GWAS on mtDNAcn, adding to the evidence of the genetic background of this trait. |
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| Item Description: | Advance access publication date 23 November 2021 Gesehen am 24.05.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1460-2083 |
| DOI: | 10.1093/hmg/ddab341 |