Association of DNA Methylation of the NLRP3 Gene with Changes in Cortical Thickness in Major Depressive Disorder
Abstract
:1. Introduction
2. Results
2.1. Differential Methylation Analysis
2.2. Cortical Thickness Analysis
2.3. Correlation between DNA Methylation and Cortical Thickness
3. Discussion
4. Materials and Methods
4.1. Participants
4.2. Methylomic Profiling of NLRP3 Gene
4.3. Genome-Wide DNA Methylation Analysis of the NRLP3 Gene
4.4. MRI Data Acquisition
4.5. Neuroimage Processing
4.6. Statistical Methods for Neuroimaging–DNA Methylation Correlation Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | MDD (n = 88) | HC (n = 74) | p-Value (t, χ2) |
---|---|---|---|
Age | 44.38 ± 13.76 | 30.46 ± 12.06 | <0.001 (t = 6.858) |
Sex (F/M) | 62/26 | 43/31 | 0.101 (χ2 = 2.687) |
Education level | |||
Elementary and middle school | 26 | 3 | <0.001 (χ2 = 17.792) |
High school or college/university | 57 | 66 | |
Above graduate school | 4 | 5 | |
HDRS-17 score | 15.47 ± 6.83 | 1.15 ± 1.90 | <0.001 (t = 18.807) |
Duration of illness (months) | 28.95 ± 45.16 | NA | NA |
Drug-naïve/Medicated patients | 32/56 | NA | NA |
Remitted/Non-remitted patients | 13/75 | NA | NA |
Medication, n | |||
SSRI | 22 | NA | NA |
SNRI | 13 | ||
NDRI | 3 | ||
NaSSA | 4 | ||
Other AD | 3 | ||
Combination of ADs | 11 | ||
AP | 12 | ||
Combination of APs | 3 |
CpG Site | Puncorr | Pcorr | Δβ | Chromosome | Position | Gene | Genomic Feature |
---|---|---|---|---|---|---|---|
cg06710101 | 0.002 | 0.015 | 0.007 | 1 | 247587253 | NLRP3 | Body |
cg09418290 | 0.004 | 0.027 | 0.001 | 1 | 247579319 | NLRP3 | TSS200 |
cg05615449 | 0.009 | 0.049 | −0.028 | 1 | 247601478 | NLRP3 | Body |
cg18126557 | 0.023 | 0.091 | 0.012 | 1 | 247611842 | NLRP3 | 3′UTR |
cg18793688 | 0.038 | 0.126 | −0.002 | 1 | 247588074 | NLRP3 | Body |
Cortical Regions | MDD | HC | F | Puncorr | Pcorr | ||
---|---|---|---|---|---|---|---|
Mean | SD | Mean | SD | ||||
MDD < HC | |||||||
L Ventral posterior cingulate gyrus | 2.15 | 0.44 | 2.45 | 0.37 | 21.116 | 8.87 × 10−6 | 0.001 |
L Middle occipital gyrus | 2.38 | 0.27 | 2.55 | 0.22 | 13.491 | 3.29 × 10−4 | 0.025 |
L Lateral occipitotemporal gyrus | 2.40 | 0.48 | 2.77 | 0.30 | 33.403 | 3.95 × 10−8 | 3.01 × 10−6 |
L Superior parietal lobule | 2.27 | 0.22 | 2.45 | 0.19 | 20.706 | 1.07 × 10−5 | 0.001 |
L Planum polare | 2.96 | 0.50 | 3.33 | 0.39 | 25.519 | 1.21 × 10−6 | 9.20 × 10−5 |
L Middle temporal gyrus | 2.67 | 0.45 | 2.96 | 0.35 | 20.095 | 1.42 × 10−5 | 0.001 |
R Ventral posterior cingulate gyrus | 2.21 | 0.44 | 2.69 | 0.33 | 48.054 | 1.03 × 10−10 | 7.85 × 10−9 |
R Short insular gyrus | 2.98 | 0.40 | 3.26 | 0.60 | 12.822 | 4.57 × 10−4 | 0.035 |
R Middle occipital gyrus | 2.45 | 0.27 | 2.60 | 0.20 | 13.169 | 3.85 × 10−4 | 0.029 |
R Lateral occipitotemporal gyrus | 2.44 | 0.41 | 2.81 | 0.28 | 35.612 | 1.56 × 10−8 | 1.19 × 10−6 |
R Superior parietal lobule | 2.28 | 0.23 | 2.43 | 0.17 | 16.383 | 8.13 × 10−5 | 0.006 |
R Precentral gyrus | 2.66 | 0.23 | 2.80 | 0.23 | 12.840 | 4.53 × 10−4 | 0.034 |
R Subcallosal gyrus | 2.37 | 0.42 | 2.70 | 0.50 | 14.193 | 2.33 × 10−4 | 0.018 |
R Planum polare | 2.87 | 0.44 | 3.16 | 0.38 | 15.408 | 1.30 × 10−4 | 0.010 |
R Middle temporal gyrus | 2.67 | 0.43 | 2.92 | 0.30 | 17.928 | 3.91 × 10−5 | 0.003 |
MDD > HC | |||||||
L Paracentral lobule | 2.52 | 0.23 | 2.44 | 0.18 | 15.162 | 1.46 × 10−4 | 0.011 |
L Posterior mid-cingulate gyrus | 2.68 | 0.19 | 2.56 | 0.23 | 23.786 | 2.63 × 10−6 | 2.00 × 10−4 |
L Cuneus | 2.20 | 0.52 | 1.94 | 0.39 | 22.871 | 3.98 × 10−6 | 3.02 × 10−4 |
L Superior occipital gyrus | 2.47 | 0.33 | 2.12 | 0.26 | 61.294 | 7.03 × 10−13 | 5.34 × 10−11 |
L Lingual gyrus | 2.37 | 0.57 | 2.03 | 0.30 | 30.837 | 1.18 × 10−7 | 8.98 × 10−6 |
L Postcentral gyrus | 2.43 | 0.34 | 2.22 | 0.19 | 33.786 | 3.36 × 10−8 | 2.56 × 10−6 |
L Precuneus | 2.64 | 0.21 | 2.55 | 0.19 | 22.229 | 5.33 × 10−6 | 4.05 × 10−4 |
L Lateral superior temporal gyrus | 3.18 | 0.30 | 3.00 | 0.30 | 22.420 | 4.88 × 10−6 | 3.71 × 10−4 |
R Frontomarginal gyrus | 2.47 | 0.26 | 2.36 | 0.23 | 12.997 | 4.19 × 10−4 | 0.032 |
R Posterior mid-cingulate gyrus | 2.71 | 0.19 | 2.59 | 0.19 | 24.728 | 1.72 × 10−6 | 1.31 × 10−4 |
R Cuneus | 2.22 | 0.54 | 1.95 | 0.40 | 23.243 | 3.36 × 10−6 | 2.56 × 10−4 |
R Superior occipital gyrus | 2.47 | 0.33 | 2.18 | 0.22 | 55.742 | 5.47 × 10−12 | 4.16 × 10−10 |
R Lingual gyrus | 2.35 | 0.53 | 2.10 | 0.29 | 26.666 | 7.28 × 10−7 | 5.53 × 10−5 |
R Postcentral gyrus | 2.42 | 0.37 | 2.22 | 0.20 | 27.926 | 4.18 × 10−7 | 3.18 × 10−5 |
R Lateral superior temporal gyrus | 3.14 | 0.24 | 2.97 | 0.36 | 18.004 | 3.77 × 10−5 | 0.003 |
R Planum temporale | 2.75 | 0.32 | 2.62 | 0.22 | 13.815 | 2.81 × 10−4 | 0.021 |
Cortical Regions | cg18793688 | cg09418290 | ||||
---|---|---|---|---|---|---|
r | Puncorr | Pcorr | r | Puncorr | Pcorr | |
L Cuneus * | −0.364 | 8.46 × 10−4 | 0.038 | 0.270 | 0.015 | 0.118 |
L Superior frontal gyrus | −0.359 | 0.001 | 0.038 | 0.272 | 0.014 | 0.118 |
L Superior occipital gyrus * | −0.276 | 0.013 | 0.118 | 0.369 | 6.87 × 10−4 | 0.037 |
L Lingual gyrus * | −0.383 | 4.19 × 10−4 | 0.037 | 0.273 | 0.014 | 0.118 |
R Cuneus * | −0.378 | 5.10 × 10−4 | 0.037 | 0.261 | 0.019 | 0.140 |
R Superior frontal gyrus | −0.388 | 3.42 × 10−4 | 0.037 | 0.238 | 0.033 | 0.191 |
R Lingual gyrus * | −0.447 | 2.94 × 10−5 | 0.011 | 0.289 | 0.009 | 0.103 |
R Postcentral gyrus * | −0.394 | 2.72 × 10−4 | 0.037 | 0.282 | 0.011 | 0.110 |
R Planum temporale * | −0.332 | 0.002 | 0.052 | 0.373 | 6.08 × 10−4 | 0.037 |
R Middle temporal gyrus † | 0.362 | 9.07 × 10−4 | 0.038 | −0.254 | 0.022 | 0.151 |
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Han, K.-M.; Choi, K.W.; Kim, A.; Kang, W.; Kang, Y.; Tae, W.-S.; Han, M.-R.; Ham, B.-J. Association of DNA Methylation of the NLRP3 Gene with Changes in Cortical Thickness in Major Depressive Disorder. Int. J. Mol. Sci. 2022, 23, 5768. https://doi.org/10.3390/ijms23105768
Han K-M, Choi KW, Kim A, Kang W, Kang Y, Tae W-S, Han M-R, Ham B-J. Association of DNA Methylation of the NLRP3 Gene with Changes in Cortical Thickness in Major Depressive Disorder. International Journal of Molecular Sciences. 2022; 23(10):5768. https://doi.org/10.3390/ijms23105768
Chicago/Turabian StyleHan, Kyu-Man, Kwan Woo Choi, Aram Kim, Wooyoung Kang, Youbin Kang, Woo-Suk Tae, Mi-Ryung Han, and Byung-Joo Ham. 2022. "Association of DNA Methylation of the NLRP3 Gene with Changes in Cortical Thickness in Major Depressive Disorder" International Journal of Molecular Sciences 23, no. 10: 5768. https://doi.org/10.3390/ijms23105768