bims-humivi Biomed News
on Human mito-nuclear genetic interplay
Issue of 2026–02–08
two papers selected by
Mariangela Santorsola, Università di Pavia
  1. Mitonuclear Discordance and Gout, Type 2 Diabetes and Chronic Kidney Disease in Aotearoa New Zealand Indigenous Māori and Pacific People.
  2. Powering the mind: deciphering the shared genetic architecture between mitochondrial DNA copy number and major psychiatric disorders.
  1. Ann Hum Genet. 2026 Feb 02.
    Mitonuclear Discordance and Gout, Type 2 Diabetes and Chronic Kidney Disease in Aotearoa New Zealand Indigenous Māori and Pacific People.
    Rachel R Dickerson, Riku Takei, Murray Cadzow, Theodore G Schurr, Phillip L Wilcox, Nicola Dalbeth, Lisa K Stamp, Rinki Murphy, Janak R de Zoysa, Stephane E Castel, Anne-Katrin Emde, Kaja A Wasik, Tony R Merriman, Anna L Gosling.
       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.
    Keywords:  New Zealand; ancestry; diabetes; gout; kidney disease; mitochondria
    DOI:  https://doi.org/10.1111/ahg.70033
  2. Mol Psychiatry. 2026 Feb 03.
    Powering the mind: deciphering the shared genetic architecture between mitochondrial DNA copy number and major psychiatric disorders.
    Hui Xue, Minghuan Lei, Qiyu Zhao, Zhihui Zhang, Zuhao Sun, Yujie Zhang, Ying Zhai, Jinglei Xu, Ying Wang, Qi An, Wenjie Cai, Linlin Jia, Shen Li, Xi-Jian Dai, Feng Liu.
      Mitochondrial DNA copy number (mtDNA-CN) reflects mitochondrial function and has been associated with several psychiatric disorders. However, the shared genetic architecture between mtDNA-CN and psychiatric conditions remains largely unexplored. Utilizing the largest available genome-wide association study (GWAS) summary statistics from individuals of European ancestry, we systematically investigated the shared genetic architecture between mtDNA-CN and five major psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ). Specifically, we assessed genetic overlap at the global, regional, and variant levels. In addition, gene expression analyses were performed to identify genes whose predicted expression was associated with both mtDNA-CN and psychiatric traits. Functional enrichment analyses were conducted to characterize the biological functions underlying the shared genes. Significant global-level genetic overlap was observed between mtDNA-CN and all five psychiatric disorders. Regional analyses identified four genomic regions with high pleiotropic probability shared between mtDNA-CN and ADHD, BD, and SCZ. At the variant level, 30 lead variants were detected, corresponding to 30 independent loci jointly associated with mtDNA-CN and psychiatric traits. These loci were mapped to 305 unique genes, among which 87 genes exhibited significant associations between their predicted expression levels and both mtDNA-CN and psychiatric disorders. Functional enrichment highlighted neurodevelopmental and ubiquitin-related pathways, with significant downregulation of shared genes in key brain regions. These findings provide comprehensive evidence for shared genetic mechanisms linking mitochondrial function and psychiatric disorders, highlighting mitochondrial dysfunction as a promising target for future therapy.
    DOI:  https://doi.org/10.1038/s41380-026-03463-0
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