1. Epidemiology and Global Health
  2. Genetics and Genomics

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

  1. Richard F Oppong
  2. Antonio Terracciano
  3. Martin Picard
  4. Yong Qian
  5. Thomas J Butler
  6. Toshiko Tanaka
  7. Ann Zenobia Moore
  8. Eleanor M Simonsick
  9. Krista Opsahl-Ong
  10. Christopher Coletta
  11. Angelina R Sutin
  12. Myriam Gorospe
  13. Susan M Resnick
  14. Francesco Cucca
  15. Sonja W Scholz
  16. Bryan J Traynor
  17. David Schlessinger
  18. Luigi Ferrucci  Is a corresponding author
  19. Jun Ding  Is a corresponding author
  1. Translational Gerontology Branch, National Institute on Aging, United States
  2. Department of Geriatrics, Florida State University, United States
  3. Laboratory of Behavioral Neuroscience, National Institute on Aging, United States
  4. Division of Behavioral Medicine, Department of Psychiatry; Merritt Center and Columbia Translational Neuroscience initiative, Department of Neurology, Columbia University Irving Medical Center; New York State Psychiatric Institute, United States
  5. Laboratory of Genetics and Genomics, National Institute on Aging, United States
  6. Department of Behavioral Sciences and Social Medicine, College of Medicine, Florida State University, United States
  7. Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Italy
  8. Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, United States
  9. Department of Neurology, Johns Hopkins University Medical Center, United States
  10. Laboratory of Neurogenetics, National Institute on Aging, United States
https://doi.org/10.7554/eLife.77806
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Cite this article
  1. Richard F Oppong
  2. Antonio Terracciano
  3. Martin Picard
  4. Yong Qian
  5. Thomas J Butler
  6. Toshiko Tanaka
  7. Ann Zenobia Moore
  8. Eleanor M Simonsick
  9. Krista Opsahl-Ong
  10. Christopher Coletta
  11. Angelina R Sutin
  12. Myriam Gorospe
  13. Susan M Resnick
  14. Francesco Cucca
  15. Sonja W Scholz
  16. Bryan J Traynor
  17. David Schlessinger
  18. Luigi Ferrucci
  19. Jun Ding
(2022)
Personality traits are consistently associated with blood mitochondrial DNA copy number estimated from genome sequences in two genetic cohort studies
eLife 11:e77806.
https://doi.org/10.7554/eLife.77806
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14 figures, 9 tables and 3 additional files

Figures

Figure 1
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Association of mitochondrial DNA copy number (mtDNAcn) with age, and sex differences.

Panel (A) is the Baltimore Longitudinal Study of Aging (BLSA) cohort, and panel (B) is the SardiNIA cohort. Plots (i) are regression of mtDNAcn residuals on age after adjusting for sex, sequence coverage, platelets count, and white blood cell parameters. Plots (ii) are comparisons of mtDNAcn residuals after adjusting for age, sequence coverage, platelets count, and white blood cell parameters between males (M) and females (F), with t-test p-values shown.

Figure 2
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Association of Revised NEO Personality Inventory (NEO-PI-R) traits with mitochondrial DNA copy number (mtDNAcn).

Standardized/pooled effects with 95% CI of NEO-PI-R traits after adjusting for the effects of age, sex, sequence coverage, platelets count, and white blood cell parameters. Color coding is green for positive personality types, red for negative personality types, and blue for the composite scores for the big five NEO-PI-R domains. * Traits with false discovery rate (FDR)-corrected meta-analysis p-values≤0.01.

Figure 3
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Comparison of mitochondrial DNA copy number (mtDNAcn) values among the five personality-mortality indices created from the vulnerability facet of Neuroticism, activity facet of Extraversion, and self-discipline and competence facets of Conscientiousness.

Panel (A) is Baltimore Longitudinal Study of Aging (BLSA) cohort, and panel (B) is SardiNIA cohort. The personality-mortality index with the lowest mortality risk is 4, and the index with the highest mortality risk is index 0. p-Values of linear regression of mtDNAcn and the personality-mortality index are shown on the plots.

Figure 4
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The effect of personality-mortality index (PMI) on mortality is significantly mediated via mitochondrial DNA copy number (mtDNAcn).

Panel (A) is a Kaplan–Meier plot of time to death of Baltimore Longitudinal Study of Aging (BLSA) participants in the five PMIs. Panel (B) shows the regression coefficients between PMI (predictor), mortality (outcome), and mtDNAcn (mediator) for the BLSA study. The effects of age and sex are adjusted for in the models. The indirect effect is (4.89) × (–0.02) = –0.097. We tested for the significance of the indirect effect using 5000 bootstrap samples and it was statistically significant (p-value=0.002). See Table 3 for more details.

Appendix 1—figure 1
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Random-effect meta-analysis of Neuroticism domain of Revised NEO Personality Inventory (NEO-PI-R).
Appendix 1—figure 2
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Comparison of effect sizes of Revised NEO Personality Inventory (NEO-PI-R) traits between the two cohorts.

Regression model adjusted for the effects of age, sex, sequence coverage, and white blood cell parameters. Color coding is green for positive personality types, red for negative personality types, and blue for the composite scores for the big five NEO-PI-R domains.

Appendix 1—figure 3
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Comparison of effect sizes of Revised NEO Personality Inventory (NEO-PI-R) traits between models with white blood cell (WBC) parameters adjustments and with no adjustments.

Panel (A) is Baltimore Longitudinal Study of Aging (BLSA) cohort, and panel (B) is SardiNIA cohort. Color coding is green for positive personality types, red for negative personality types, and blue for the composite scores for the big five NEO-PI-R domains.

Appendix 1—figure 4
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Comparison of mitochondrial DNA copy number (mtDNAcn) values among the four distinct personality types created from the vulnerability facet of Neuroticism and self-discipline facet of Conscientiousness.

Panel (A) is Baltimore Longitudinal Study of Aging (BLSA) cohort, and panel (B) is SardiNIA cohort. The personality type with lowest mortality risk (low vulnerability high self-discipline [LVHD]) has a significantly higher mean mtDNAcn value than the highest mortality risk type (high vulnerability low self-discipline [HVLD]).

Appendix 1—figure 5
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Stability of Revised NEO Personality Inventory (NEO-PI-R) traits across multiple visits.

(A) Test–retest stability of the NEO-PI-R traits. Red dash line is Pearson’s correlation of 0.8. All the traits have a high test–retest reliability. (B) The stability of two randomly selected personality traits (Deliberation and Activity) across multiple measurement visits. Plot color represents starting trait values; blue shows individual’s lower initial trait values, and red shows higher initial trait values. The plot shows that subsequent trait measurement tends to stabilize around the initial measurement values.

Appendix 1—figure 6
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Correlation between Revised NEO Personality Inventory (NEO-PI-R) traits.

The color intensity and size of circles are indications of the size and significance of the correlation.

Appendix 1—figure 7
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Histograms of autosomal and mitochondrial DNA (mtDNA) sequencing coverages for (A) Baltimore Longitudinal Study of Aging (BLSA) and (B) SardiNIA.
Appendix 1—figure 8
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Four distinct personality types are created from the vulnerability facet of Neuroticism and the self-discipline facet of Conscientiousness.
Appendix 1—figure 9
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Mitochondrial DNA copy number (mtDNAcn) comparison between menopausal and premenopausal women in SardiNIA.
Appendix 1—figure 10
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Mitochondrial DNA copy number (mtDNAcn) comparison between the major mitochondrial haplogroups present in more than five study participants.

Tables

Table 1
Demography of study cohorts.
BLSA (n = 722)SardiNIA (n = 587)
n/%/mean (SD)n/%/mean (SD)
Female48.1%62.2%
Age (years)74.88 (10.86)57.28 (13.24)
Education (years)17.68 (2.50)7.33 (3.96)
Big five personality traits
Neuroticism45.35 (8.25)55.46 (8.36)
Extraversion50.60 (10.10)46.80 (8.04)
Openness52.59 (10.55)44.35 (9.08)
Agreeableness51.88 (9.51)47.55 (8.55)
Conscientiousness51.91 (9.31)49.20 (8.79)
Measures of depressive symptoms
CES-D continuous5.47 (5.66)11.66 (7.79)
CES-D binary cutoff 166.6%23.8%
CES-D binary cutoff 202.6%13.9%

  1. BLSA, Baltimore Longitudinal Study of Aging; CES-D, Center for Epidemiologic Studies Depression Scale.

Table 2
Association of Neuroticism domain with mitochondrial DNA copy number (mtDNAcn).
Domain and facetsBLSA β (p-value)SardiNIA β (p-value)Pooled β (p-value)*I2 % [p of Q]
Neuroticism–0.106 (0.001)–0.116 (0.01)–0.11 (0.0015)0% [0.87]
Anxiety–0.082 (0.01)–0.086 (0.08)–0.08 (0.010)0% [0.94]
Angry hostility–0.078 (0.02)–0.090 (0.054)–0.08 (0.010)0% [0.84]
Depression–0.122 (0.0002)–0.070 (0.1)–0.11 (0.0015)0% [0.37]
Self-consciousness–0.060 (0.08)–0.116 (0.01)–0.08 (0.013)0% [0.33]
Impulsiveness–0.067 (0.046)–0.023 (0.6)–0.05 (0.099)0% [0.45]
Vulnerability–0.080 (0.02)–0.097 (0.04)–0.09 (0.0087)0% [0.77]
Measures of depressive symptoms
CES-D continuous–0.122 (0.0002)–0.077 (0.13)–0.11 (0.00008)0% [0.46]
CES-D binary cutoff 16–0.260 (0.051)–0.180 (0.13)–0.22 (0.015)0% [0.65]
CES-D binary cutoff 20–0.591 (0.005)–0.343 (0.02)–0.42 (0.0004)0% [0.34]
PMI
Personality-mortality index0.092 (0.005)0.124 (0.007)0.10 (0.0001)0% [0.57]
 

  1. BLSA, Baltimore Longitudinal Study of Aging; CES-D, Center for Epidemiologic Studies Depression Scale; PMI, personality-mortality index; FDR, false discovery rate.

  2. *

    Pooled effect p-values of Neuroticism domain and facets are FDR-corrected for 35 tests for 35 personality traits. Information for other personality domains and facets are provided in Appendix 1—table 2.

Table 3
Testing the direct and indirect effects of personality-mortality index and mitochondrial DNA copy number (mtDNAcn) on mortality.
BLSA (n = 721)SardiNIA (n = 395)
Total effectEstimate (p-value)Estimate (p-value)
Personality-mortality index–0.149 (0.001)–0.022 (0.808)
Full effects
Personality-mortality index–0.052 (0.260)–0.019 (0.895)
mtDNAcn–0.020 (0.000)–0.001 (0.966)
Indirect effectEstimate [nonparametric bootstrap 95% CI]Estimate [nonparametric bootstrap 95% CI]
mtDNAcn–0.097 [–0.143; –0.03]–0.004 [–0.169; 0.189]

  1. BLSA, Baltimore Longitudinal Study of Aging.

Appendix 1—table 1
Association of age, sex, and white blood cell (WBC) parameters with mitochondrial DNA copy number (mtDNAcn).
β (p-value) of model adjusted
No adjustmentAge, sex, coverage, and WBC parameters
TraitBLSASardiNIABLSASardiNIA
Age–0.025 (2.85e-13)–0.0093 (0.003)–0.014 (2.52e-5)–0.0065 (0.028)
Sex–0.61 (8.14e-17)–0.25 (0.004)–0.36 (1.21e-6)–0.13 (0.11)
Platelet count0.004 (1.31e-7)0.0007 (0.30)0.003 (3.71e-6)0.001 (0.063)
WBC count–0.13 (2.35e-10)–0.14 (1.37e-8)–0.097 (1.48e-6)–0.08 (0.002)
Lymphocytes percent0.04 (5.5e-25)0.042 (5.19e-16)–0.033 (0.23)0.073 (0.55)
Neutrophils percent–0.041 (1.47e-28)–0.041 (6.19e-18)–0.063 (0.021)0.036 (0.77)
Eosinophils percent0.037 (0.031)0.043 (0.06)–0.045 (0.16)0.076 (0.55)
Monocytes percent0.022 (0.082)0.062 (0.002)–0.014 (0.57)0.082 (0.52)
Basophils percent0.44 (8.54e-5)0.11 (0.38)0.044 (0.69)–0.076 (0.55)

  1. BLSA, Baltimore Longitudinal Study of Aging.

Appendix 1—table 2
Association of Revised NEO Personality Inventory (NEO-PI-R) domains with mitochondrial DNA copy number (mtDNAcn).
NEO-PI-R domainsBLSA β (p-value)SardiNIA β (p-value)Meta-analysis
Pooled βRaw p-valueFDR adj. p*I2 % [p of Q]
Neuroticism–0.106 (0.001)–0.116 (0.01)–0.110.000060.00150% [0.87]
Anxiety–0.082 (0.01)–0.086 (0.08)–0.080.0020.0100% [0.94]
Angry hostility–0.078 (0.02)–0.090 (0.054)–0.080.0030.0100% [0.84]
Depression–0.122 (0.0002)–0.070 (0.1)–0.110.000080.00150% [0.37]
Self-consciousness–0.060 (0.08)–0.116 (0.01)–0.080.0040.0130% [0.33]
Impulsiveness–0.067 (0.046)–0.023 (0.6)–0.050.060.0990% [0.45]
Vulnerability–0.080 (0.02)–0.097 (0.04)–0.090.0020.00870% [0.77]
Extraversion0.083 (0.01)0.117 (0.01)0.090.00050.00360% [0.56]
Warmth0.064 (0.06)0.162 (0.0004)0.110.030.05166% [0.09]
Gregariousness0.040 (0.2)0.047 (0.3)0.040.10.160% [0.90]
Assertiveness0.066 (0.048)–0.007 (0.9)0.040.30.3638% [0.21]
Activity0.106 (0.002)0.037 (0.4)0.080.020.04030% [0.23]
Excitement seeking0.011 (0.7)0.067 (0.2)0.030.30.360% [0.35]
Positive emotions0.087 (0.01)0.122 (0.01)0.100.00040.00360% [0.54]
Openness0.066 (0.06)0.076 (0.1)0.070.010.0320% [0.86]
Fantasy–0.006 (0.9)0.093 (0.051)0.040.40.4865% [0.09]
Aesthetics0.015 (0.7)0.086 (0.06)0.040.20.2734% [0.22]
Feelings0.045 (0.2)–0.015 (0.8)0.020.40.472% [0.31]
Actions0.063 (0.07)0.039 (0.4)0.050.0510.0940% [0.68]
Ideas0.079 (0.02)0.070 (0.1)0.080.0050.0140% [0.88]
Values0.078 (0.02)–0.014 (0.8)0.040.40.4659% [0.12]
Agreeableness0.058 (0.1)0.141 (0.003)0.090.020.04749% [0.16]
Trust0.085 (0.014)0.065 (0.2)0.080.0050.0140% [0.73]
Straightforwardness0.059 (0.08)0.095 (0.04)0.070.0090.0240% [0.54]
Altruism0.077 (0.02)0.133 (0.005)0.100.00050.00360% [0.34]
Compliance0.005 (0.9)0.039 (0.4)0.020.50.570% [0.57]
Modesty–0.018 (0.6)0.080 (0.09)0.030.60.6265% [0.09]
Tendermindedness0.030 (0.4)0.089 (0.053)0.050.070.127% [0.30]
Conscientiousness0.084 (0.009)0.040 (0.4)0.070.0080.0220% [0.43]
Competence0.115 (0.0004)0.024 (0.6)0.080.090.1461% [0.11]
Order–0.003 (0.9)0.036 (0.4)0.010.70.690% [0.49]
Dutifulness0.097 (0.003)0.066 (0.2)0.090.0010.00640% [0.57]
Achievement striving0.093 (0.005)0.018 (0.7)0.060.090.1442% [0.19]
Self-discipline0.056 (0.08)0.016 (0.7)0.040.10.140% [0.48]
Deliberation0.069 (0.03)0.009 (0.8)0.050.090.1411% [0.29]
Personality and mortalityBLSA Md (p-value)SardiNIA Md (p-value)Pooled MdRaw p-valueFDR adj. pI2 % [p of Q]
HVLD vs. LVHD0.234 (0.006)0.209 (0.09)0.2260.0013-0% [0.87]

  1. BLSA, Baltimore Longitudinal Study of Aging; HVLD, high vulnerability low self-discipline; LVHD, low vulnerability high self-discipline; FDR, false discovery rate.

  2. *

    Entries with FDR-corrected p-values≤0.01 are labeled as bold.

Appendix 1—table 3
Cox proportional hazards analysis of four Revised NEO Personality Inventory (NEO-PI-R) traits used to compute personality-mortality index (PMI).

Models adjusted for the effect of age and sex.

CoefficientHazard ratiop-Value
Vulnerability0.0371.0380.0006
Activity–0.0360.9460.0004
Self-discipline–0.0280.9720.002
Competence–0.0410.9592.28e-5
Appendix 1—table 4
Testing the direct and indirect effects of mitochondrial DNA copy number (mtDNAcn) and personality-mortality index (PMI) on mortality.
BLSA (n = 721)SardiNIA (n = 395)
Total effectEstimate (p-value)Estimate (p-value)
 mtDNAcn–0.010 (0.001)0.003 (0.574)
Full effects
 mtDNAcn–0.010 (0.000)0.003 (0.673)
 PMI–0.118 (0.340)–0.028 (0.959)
Indirect effectEstimate (nonparametric bootstrap p-value)Estimate (nonparametric bootstrap p-value)
 PMI0.000 (0.355)0.000 (0.963)

  1. BLSA, Baltimore Longitudinal Study of Aging.

Appendix 1—table 5
Association of Revised NEO Personality Inventory (NEO-PI-R) domains with mitochondrial DNA copy number (mtDNAcn) in SardiNIA women, with and without adjustment for menopause status.

Both models adjusted for the effect of age, sequence coverage, white blood cell (WBC), platelet count, and percentages of major leukocytes.

β (p-value) of model
NEO-PI-R domainsNot adjusted for menopause statusAdjusted for menopause status
Neuroticism–0.013 (0.074)–0.013 (0.077)
Anxiety–0.007 (0.316)–0.007 (0.323)
Angry hostility–0.010 (0.123)–0.010 (0.127)
Depression–0.008 (0.236)–0.008 (0.240)
Self-consciousness–0.012 (0.056)–0.012 (0.056)
Impulsiveness0.002 (0.794)0.002 (0.802)
Vulnerability–0.011 (0.059)–0.011 (0.063)
Extraversion0.017 (0.022)0.017 (0.021)
Warmth0.021 (0.0004)0.021 (0.0004)
Gregariousness0.005 (0.483)0.005 (0.476)
Assertiveness0.002 (0.828)0.001 (0.862)
Activity0.001 (0.857)0.001 (0.864)
Excitement seeking0.010 (0.183)0.010 (0.165)
Positive emotions0.014 (0.020)0.015 (0.017)
Openness0.014 (0.035)0.014 (0.036)
Fantasy0.017 (0.016)0.017 (0.016)
Aesthetics0.011 (0.098)0.011 (0.102)
Feelings0.007 (0.319)0.007 (0.312)
Actions0.008 (0.195)0.008 (0.192)
Ideas0.009 (0.189)0.009 (0.186)
Values0.001 (0.887)0.001 (0.910)
Agreeableness0.017 (0.010)0.017 (0.011)
Trust0.006 (0.313)0.006 (0.321)
Straightforwardness0.012 (0.050)0.012 (0.055)
Altruism0.012 (0.042)0.012 (0.041)
Compliance0.008 (0.175)0.008 (0.179)
Modesty0.005 (0.471)0.005 (0.499)
Tendermindedness0.013 (0.025)0.013 (0.024)
Conscientiousness0.006 (0.409)0.005 (0.428)
Competence0.001 (0.846)0.001 (0.857)
Order0.003 (0.606)0.003 (0.637)
Dutifulness0.006 (0.325)0.006 (0.346)
Achievement striving0.005 (0.471)0.005 (0.442)
Self-discipline0.001 (0.854)0.001 (0.908)
Deliberation0.005 (0.414)0.005 (0.417)
Appendix 1—table 6
Effect of mitochondrial haplogroups on mitochondrial DNA copy number (mtDNAcn).
HaplogroupsFrequency (%)BetaSEp-Value
N1.94–0.450.270.095
H41.83–0.120.080.103
T9.420.200.130.122
X1.94–0.310.270.258
K9.700.120.130.361
W2.490.190.240.418
V3.88–0.130.190.500
U12.600.070.110.504
I2.77–0.090.230.703
J11.500.030.120.795

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A checklist of items that should be included in reports of observational studies.

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Source code 1

R code for the analysis on mtDNAcn and personality.

https://cdn.elifesciences.org/articles/77806/elife-77806-code1-v1.zip

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  1. Richard F Oppong
  2. Antonio Terracciano
  3. Martin Picard
  4. Yong Qian
  5. Thomas J Butler
  6. Toshiko Tanaka
  7. Ann Zenobia Moore
  8. Eleanor M Simonsick
  9. Krista Opsahl-Ong
  10. Christopher Coletta
  11. Angelina R Sutin
  12. Myriam Gorospe
  13. Susan M Resnick
  14. Francesco Cucca
  15. Sonja W Scholz
  16. Bryan J Traynor
  17. David Schlessinger
  18. Luigi Ferrucci
  19. Jun Ding
(2022)
Personality traits are consistently associated with blood mitochondrial DNA copy number estimated from genome sequences in two genetic cohort studies
eLife 11:e77806.
https://doi.org/10.7554/eLife.77806