ABSTRACT
Background
Mitochondrial proteins are encoded by both mitochondrial- and nuclear-encoded genes. Because mitochondrial DNA (mtDNA) is maternally inherited, admixed individuals may have different ancestral sources for their nuclear and mitochondrial genomes. The potential incompatibility between these genomic components may cause suboptimal mitochondrial function and result in energy-related pathologies. This incompatibility, or ‘mitonuclear discordance’, is defined as the proportion of the nuclear genome not derived from the same ancestral source as the mtDNA.
Methods
Based on this understanding, we hypothesized that increased mitonuclear discordance would be associated with lower mitochondrial copy number and increased risk of gout, type 2 diabetes and chronic kidney disease. We tested this prediction using genomic data from a cohort of 2301 New Zealanders with Polynesian ancestry (Indigenous Māori and Pacific peoples living in Aotearoa New Zealand).
Results
We observed that increased mitonuclear discordance was correlated with a decreased chance of gout (p = 5.08 × 10−5) and a decreased chance of diagnosis with type 2 diabetes, specifically in individuals having haplogroup B4a1a (p = 4.20 × 10−9), which was present in 86.0% of the Polynesian study cohort. No significant association was found between mitonuclear discordance and mitochondrial copy number (p = 0.93), risk of chronic kidney disease (p = 0.084) or gout flare frequency (p = 0.53).
Conclusion
Overall, while these results contradicted our hypothesis, they can potentially be explained by a higher prevalence of disease-associated alleles for gout and type 2 diabetes in Polynesian genomes.