Personality traits are consistently associated with blood mitochondrial DNA copy number estimated from genome sequences in two genetic cohort studies

• Published in: eLife 2022-12, Vol.11
• Main Authors: Oppong, Richard F, Terracciano, Antonio, Picard, Martin, Qian, Yong, Butler, Thomas J, Tanaka, Toshiko, Moore, Ann Zenobia, Simonsick, Eleanor M, Opsahl-Ong, Krista, Coletta, Christopher, Sutin, Angelina R, Gorospe, Myriam, Resnick, Susan M, Cucca, Francesco, Scholz, Sonja W, Traynor, Bryan J, Schlessinger, David, Ferrucci, Luigi, Ding, Jun
• Format: Article
• Language: English
• Subjects: Aging; Alzheimer's disease; Biomarkers; Blood; Cohort analysis; Copy number; Dementia; Depressive Disorder, Major; depressive symptoms; Diabetes; Diabetes mellitus; DNA Copy Number Variations; DNA, Mitochondrial - genetics; Epidemiology; Epidemiology and Global Health; Genetics and Genomics; genome sequence; Genomes; Humans; Hypotheses; Likert scale; Longevity; Longitudinal Studies; Mental depression; Mitochondrial DNA; mitochondrial DNA copy number; Mortality; mortality risk; Neurological diseases; Neurosis; Nucleotide sequence; Personality; Personality traits; Review boards; Stress; Whole genome sequencing
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/ELIFE.77806

Mitochondrial DNA copy number (mtDNAcn) in tissues and blood can be altered in conditions like diabetes and major depression and may play a role in aging and longevity. However, little is known about the association between mtDNAcn and personality traits linked to emotional states, metabolic health, and longevity. This study tests the hypothesis that blood mtDNAcn is related to personality traits and mediates the association between personality and mortality. We assessed the big five personality domains and facets using the Revised NEO Personality Inventory (NEO-PI-R), assessed depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D), estimated mtDNAcn levels from whole-genome sequencing, and tracked mortality in participants from the Baltimore Longitudinal Study of Aging. Results were replicated in the SardiNIA Project. We found that mtDNAcn was negatively associated with the Neuroticism domain and its facets and positively associated with facets from the other four domains. The direction and size of the effects were replicated in the SardiNIA cohort and were robust to adjustment for potential confounders in both samples. Consistent with the Neuroticism finding, higher depressive symptoms were associated with lower mtDNAcn. Finally, mtDNAcn mediated the association between personality and mortality risk. To our knowledge, this is the first study to show a replicable association between mtDNAcn and personality. Furthermore, the results support our hypothesis that mtDNAcn is a biomarker of the biological process that explains part of the association between personality and mortality. Support for this work was provided by the Intramural Research Program of the National Institute on Aging (Z01-AG000693, Z01-AG000970, and Z01-AG000949) and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health. AT was also supported by the National Institute on Aging of the National Institutes of Health Grant R01AG068093.