Year: 2023
Type: article
Abstract: Background Mitochondrial dysfunction is a hallmark of aging and manifests in age‐associated disorders, including neurodegenerative diseases. Previous work on mitochondrial DNA variants and neurocognitive outcomes has been limited to known variants of interest. Method We sequenced the mitochondrial genome in buffy coat samples from two studies, LIFE (Lifestyle Interventions and Independence for Elders) and HABC (Health Aging and Body Composition), and examined the association of shared common variants and cognitive function, after adjustment for 10 principal components to account for population stratification. Participants included self‐reported Black (n = 229 in LIFE and 393 in HABC) and White (n = 1134 in LIFE and 395 in HABC) adults aged ≥ 70 years. Cognitive function was measured by the digit‐symbol substitution test (DSST), a measure of processing speed, and the Modified Mini‐Mental State Exam (3MSE), a measure of global cognition. Result There were 96 variants which had a minor‐allele frequency ≥5% in both studies. There were 8 variants associated with DSST in White participants LIFE at the p<0.05 level and 1 at the Bonferroni‐adjusted level (m16223ct). Four reached statistical significance at the p<0.05 level in meta‐analyses of LIFE and HABC (m16223ct, m16093tc, m10873tc, m3106cnc). There were 7 variants associated with 3MSE in White participants in LIFE at the p<0.05 level and none at the Bonferroni‐adjusted level. One reached statistical significance at the p<0.05 level in meta‐analyses of LIFE and HABC (m10873tc). In Black participants, the variants had differential associations with the cognitive outcomes by study, and no associations reached statistical significance after Bonferroni correction or in meta‐analysis. The 4 variants of interest in White participants are located in the 1) hypervariable region 1 of the D‐loop (m16093tc, m16223ct), 2) gene MT‐ND4 coding for subunit ND4 of complex 1 (m10873tc), and 3) gene MT‐RNR2 coding for the 16S ribosomal RNA (m3106cnc). Conclusion Previous work has identified associations between m16223ct and hippocampal sclerosis and endurance capacity; and ND4 variants and Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and Leigh’s disease. In addition, the m10873tc ND4 coding variant is a defining mutation for European Haplogroup N. Mitochondrial genetics may contribute to cognitive health. More research is needed on mitochondrial genetics among Black individuals.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.077291
Authors: Michelle Odden, Yongmei Li, Vasantha Jotwani, Lea McGeever, Robyn Jones, Pierre‐Yves Desprez, Gregory J. Tranah
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4390200469