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Interactions between nuclear and mitochondrial SNPs and Parkinson's disease risk

Lookup NU author(s): Dr Sarah PickettORCiD, Dr Dasha Deen, Dr Angela Pyle, Dr Mauro Santibanez Koref, Dr Gavin Hudson


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© 2022. Interactions between the products of the nuclear and mitochondrial genomes are critical for the function of most eukaryotic cells. Recently the introduction of mitochondrial replacement therapy has raised the question of incompatibilities between mitochondrial and nuclear variants, and their potential influence on the genetic makeup of human populations. Such interactions could also contribute to the variability of the penetrance of pathogenic DNA variants. This led us to investigate the frequencies of combinations of nuclear and mitochondrial SNP alleles (mitonuclear combinations) in healthy individuals (n = 5375) and in a cohort of patients with Parkinson's disease (PD, n = 2210). In the unaffected population, we were not able to find associations between nuclear and mitochondrial variants with a false discovery rate below 0.05 after accounting for multiple testing (i.e., the number of combinations examined). However, in the PD cohort, five combinations surpassed this threshold. Next, after combining both cohorts, we investigated whether these associations were modulated by disease status. All five combinations were significant (p < 10−3 for all tests). These combinations also showed significant evidence for an effect of the interaction between the mitochondrial and nuclear variants on disease risk. Their nuclear components mapped to TBCA, NIBAN3, and GLT25D1 and an uncharacterised intergenic region. In summary, starting from a single cohort design we identified combinations of nuclear and mitochondrial variants affecting PD disease risk.

Publication metadata

Author(s): Pickett SJ, Deen D, Pyle A, Santibanez-Koref M, Hudson G

Publication type: Article

Publication status: Published

Journal: Mitochondrion

Year: 2022

Volume: 63

Pages: 85-88

Print publication date: 01/03/2022

Online publication date: 12/02/2022

Acceptance date: 09/02/2022

Date deposited: 17/03/2022

ISSN (print): 1567-7249

ISSN (electronic): 1872-8278

Publisher: Elsevier B.V.


DOI: 10.1016/j.mito.2022.02.002

PubMed id: 35167983


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