Causal Relationship between Aging and Anorexia Nervosa: A White-Matter-Microstructure-Mediated Mendelian Randomization Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Data Source
2.2. IVs Selection
2.3. MR Analysis
2.4. Sensitivity Analysis
2.5. Evaluation of Mediated Effects
3. Results
3.1. Direct MR Analysis and Sensitivity Analysis
3.2. Two-Step MR Analysis
3.3. Two-Step Sensitivity Analysis
3.4. Calculation of Mediation Effect
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
Name of Parameter | Brief Description | Common Interpretation |
---|---|---|
Fractional anisotropy (FA) | A scalar value describing the degree of anisotropy of a diffusion process, ranging from 0 (isotropic diffusion, no directionality) to 1 (highly anisotropic diffusion, strong directionality). | Commonly used to assess white matter integrity. Higher FA values are associated with greater fiber density, axonal diameter, and myelination. Lower FA values can indicate white matter damage or degeneration [102]. |
Intra-Cellular Volume Fraction (ICVF) | The fraction of water diffusion restricted within intra-neurite compartments, reflecting neuronal density and dendritic complexity. | Changes in ICVF can reflect pathological conditions such as neuroinflammation or neurodegeneration. Higher ICVF values suggest greater cellular density, which can be indicative of healthy neural tissue [103]. |
Isotropic Volume Fraction (ISOVF) | The fraction of water diffusion that is isotropic or hindered within tissues. | Higher ISOVF values may indicate increased tissue damage, edema, or isotropic diffusion due to reduced tissue integrity [104]. |
Principal eigenvalue or axial diffusivity (L1) | The magnitude of water diffusion along the primary direction within a voxel. | Changes in axial diffusivity can indicate axonal injury or alterations in myelin sheath integrity, providing specific information on white matter pathology [105]. |
Secondary eigenvalue (L2) | The magnitude of water diffusion perpendicular to the principal direction. | Secondary eigenvalue changes can reflect alterations in tissue integrity and may be indicative of more diffuse tissue damage, particularly in regions with complex fiber orientations [105]. |
Tertiary eigenvalue (L3) | The magnitude of water diffusion in the direction with the least diffusion. | Like the secondary eigenvalue, changes in the tertiary eigenvalue can help characterize the microstructural complexity of the tissue, especially in areas with crossing fibers [105]. |
Mean diffusivity (MD) | The average magnitude of water diffusion within a voxel, irrespective of direction. | Increased MD values are generally associated with tissue pathology such as cell swelling, edema, or decreased cell density, while decreased MD may suggest increased tissue organization or coherence [106]. |
Mode of Anisotropy (MO) | The shape of diffusion tensor ellipsoids within tissues. | Different modes of anisotropy (e.g., planar, linear, spherical) provide insights into tissue microstructure changes and organization, aiding in the characterization of white matter tracts and pathology [102]. |
Orientation Dispersion (OD) | The variability in fiber orientation within a voxel. | Higher orientation dispersion values indicate less coherent fiber orientations within a voxel, which may occur in regions with crossing fibers or disrupted white matter architecture [107]. |
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Method | Test | Validation | ||||||
---|---|---|---|---|---|---|---|---|
Nsnp | p-Value | OR | 95%CI | Nsnp | p-Value | OR | 95%CI | |
MR–Egger | 109 | 6.35 × 10−1 | 9.43 × 10−1 | 0.74–1.20 | 144 | 4.90 × 10−2 | 3.92 × 10−1 | 0.16–0.99 |
Weighted median | 109 | 1.21 × 10−1 | 8.54 × 10−1 | 0.70–1.04 | 144 | 4.94 × 10−2 | 4.31 × 10−1 | 0.19–1.00 |
IVW | 109 | 1.74 × 10−2 a | 8.51 × 10−1 | 0.75–0.97 | 144 | 7.36 × 10−3 b | 5.02 × 10−1 | 0.30–0.83 |
Simple mode | 109 | 9.89 × 10−1 | 9.97 × 10−1 | 0.67–1.48 | 144 | 4.48 × 10−1 | 5.18 × 10−1 | 0.10–2.82 |
Weighted mode | 109 | 2.91 × 10−1 | 8.91 × 10−1 | 0.72–1.10 | 144 | 2.13 × 10−1 | 5.18 × 10−1 | 0.19–1.45 |
dMRI Phenotypes | Step1 | Step2 | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Region | Phenotypes | Methods | Ppe | MRSr | phet | pple | psteiger | phet | pple | psteiger |
Internal capsule (L) | FA | TBSS | 4.68 × 10−8 | 2.04 × 10−1 | 3.40 × 10−1 | 6.10 × 10−2 | 1.37 × 10−65 | 2.23 × 10−1 | 9.19 × 10−1 | 1.19 × 10−55 |
Internal capsule (R) | FA | TBSS | 8.12 × 10−7 | 1.69 × 10−1 | 4.44 × 10−1 | 6.25 × 10−2 | 2.50 × 10−71 | 5.33 × 10−1 | 9.64 × 10−1 | 3.80 × 10−31 |
Cingulum cingulate gyrus (L) | FA | TBSS | 1.67 × 10−3 | 7.46 × 10−2 | 9.75 × 10−1 | 2.71 × 10−1 | 7.05 × 10−77 | 1.23 × 10−1 | 9.45 × 10−1 | 6.87 × 10−41 |
Cingulum cingulate gyrus (L) | FA | PXTB | 6.54 × 10−4 | 8.39 × 10−2 | 8.57 × 10−1 | 8.69 × 10−1 | 3.86 × 10−80 | 6.87 × 10−1 | 8.89 × 10−1 | 5.56 × 10−28 |
Forceps minor (L) | FA | PXTB | 8.81 × 10−4 | 8.19 × 10−2 | 1.59 × 10−1 | 1.13 × 10−1 | 1.01 × 10−64 | 5.85 × 10−1 | 8.31 × 10−1 | 6.40 × 10−127 |
Internal capsule (L) | MD | TBSS | 1.84 × 10−3 | 7.22 × 10−2 | 2.27 × 10−1 | 9.32 × 10−2 | 4.10 × 10−57 | 4.43 × 10−1 | 9.69 × 10−1 | 1.78 × 10−97 |
Anterior corona radiata (R) | MD | TBSS | 2.80 × 10−2 | 3.77 × 10−2 | 8.16 × 10−1 | 3.40 × 10−1 | 5.94 × 10−65 | 7.11 × 10−1 | 8.50 × 10−1 | 4.17 × 10−147 |
Posterior corona radiata (R) | MD | TBSS | 3.94 × 10−4 | 9.52 × 10−2 | 8.97 × 10−1 | 8.95 × 10−1 | 6.33 × 10−67 | 8.03 × 10−2 | 5.57 × 10−1 | 2.48 × 10−85 |
Posterior thalamic radiation (R) | L1 | TBSS | 6.02 × 10−3 | 5.84 × 10−2 | 4.05 × 10−1 | 1.15 × 10−1 | 1.71 × 10−63 | 1.19 × 10−1 | 9.15 × 10−1 | 1.76 × 10−33 |
Superior longitudinal fasciculus (L) | L1 | TBSS | 5.45 × 10−5 | 1.24 × 10−1 | 7.23 × 10−1 | 9.67 × 10−1 | 8.76 × 10−68 | 5.62 × 10−2 | 6.35 × 10−1 | 4.48 × 10−68 |
Internal capsule (L) | L2 | TBSS | 7.95 × 10−7 | 1.72 × 10−1 | 5.22 × 10−1 | 5.52 × 10−2 | 4.45 × 10−63 | 2.97 × 10−1 | 7.89 × 10−1 | 2.34 × 10−49 |
Posterior corona radiata (R) | L2 | TBSS | 1.27 × 10−5 | 1.39 × 10−1 | 3.17 × 10−1 | 7.28 × 10−1 | 4.34 × 10−63 | 8.45 × 10−1 | 9.72 × 10−1 | 5.04 × 10−79 |
Posterior corona radiata (L) | L2 | TBSS | 4.00 × 10−4 | 9.43 × 10−2 | 3.73 × 10−1 | 3.41 × 10−1 | 1.91 × 10−61 | 6.40 × 10−1 | 7.81 × 10−1 | 2.18 × 10−84 |
Internal capsule (L) | L3 | TBSS | 4.16 × 10−4 | 9.17 × 10−2 | 6.08 × 10−1 | 8.96 × 10−2 | 6.53 × 10−70 | 1.46 × 10−1 | 6.29 × 10−1 | 2.26 × 10−84 |
Internal capsule (L) | ICVF | TBSS | 2.14 × 10−5 | 1.33 × 10−1 | 2.80 × 10−1 | 9.49 × 10−2 | 1.25 × 10−58 | 2.25 × 10−1 | 8.52 × 10−2 | 1.66 × 10−233 |
Posterior corona radiata (R) | ICVF | TBSS | 1.72 × 10−2 | 4.26 × 10−2 | 6.93 × 10−1 | 7.17 × 10−1 | 2.80 × 10−70 | 4.45 × 10−1 | 7.87 × 10−1 | 3.60 × 10−147 |
inferior longitudinal fasciculus (L) | ICVF | PXTB | 2.13 × 10−4 | 1.03 × 10−1 | 6.40 × 10−1 | 5.90 × 10−2 | 4.33 × 10−63 | 1.95 × 10−1 | 6.90 × 10−1 | 7.95 × 10−259 |
Posterior thalamic radiation (L) | ICVF | PXTB | 1.05 × 10−3 | 8.40 × 10−2 | 7.33 × 10−1 | 5.29 × 10−2 | 1.28 × 10−64 | 9.23 × 10−2 | 2.79 × 10−1 | 2.02 × 10−183 |
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Qiu, H.; Shi, M.; Zhong, Z.; Hu, H.; Sang, H.; Zhou, M.; Feng, Z. Causal Relationship between Aging and Anorexia Nervosa: A White-Matter-Microstructure-Mediated Mendelian Randomization Analysis. Biomedicines 2024, 12, 1874. https://doi.org/10.3390/biomedicines12081874
Qiu H, Shi M, Zhong Z, Hu H, Sang H, Zhou M, Feng Z. Causal Relationship between Aging and Anorexia Nervosa: A White-Matter-Microstructure-Mediated Mendelian Randomization Analysis. Biomedicines. 2024; 12(8):1874. https://doi.org/10.3390/biomedicines12081874
Chicago/Turabian StyleQiu, Haoyuan, Miao Shi, Zicheng Zhong, Haoran Hu, Hunini Sang, Meijuan Zhou, and Zhijun Feng. 2024. "Causal Relationship between Aging and Anorexia Nervosa: A White-Matter-Microstructure-Mediated Mendelian Randomization Analysis" Biomedicines 12, no. 8: 1874. https://doi.org/10.3390/biomedicines12081874