| Title: | Linking kidney impairment to amygdala volume changes and mental disorders: a Mendelian randomization study |
| Journal: | Kidney Research and Clinical Practice |
| Published: | 15 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42299453/ |
| DOI: | https://doi.org/10.23876/j.krcp.25.282 |
| URL: | https://www.krcp-ksn.org/upload/pdf/j-krcp-25-282.pdf |
Publication 20630
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Abstract
Background: Mental disorders are highly prevalent among patients with chronic kidney disease (CKD); however, the causal effects of kidney dysfunction on specific brain volume traits and mental disorders remain underexplored.</p>
Methods: In this Mendelian randomization (MR) study, genetic instruments for kidney function and CKD, derived from genome-wide association studies (GWAS) in Chronic Kidney Disease Genetics and the UK Biobank (n = 1,201,909), were utilized for two-sample MR analysis in the discovery phase. Summary-level data from these GWAS provided exposure-outcome associations to calculate causal estimates using the inverse variance weighted method. Validation analysis was conducted using one-sample MR with individual-level data from the UK Biobank.</p>
Results: Two-sample MR identified causal associations (odds ratios [ORs] as point estimates) between estimated glomerular filtration rate (exposures) and amygdala traits (outcomes), with ORs ranging from 0.559 to 0.723 (p < 0.05). Two-sample MR between CKD (exposures) and amygdala volume traits (outcomes) reported ORs ranging from 1.042 to 1.059 (p < 0.05). These associations also linked kidney dysfunction to an increased risk of depression, using two-sample MR across 507 brain volume and 242 mental disorder GWAS datasets. Leave-one-out analyses and pleiotropy tests, including MR Egger, supported the robustness of these findings. Validation analysis confirmed reproducibility using one-sample MR.</p>
Conclusion: Our results demonstrate that kidney dysfunction causally alters amygdala volume, increasing susceptibility to mental disorders such as depression. These findings highlight the kidney-brain axis and underscore the importance of integrating mental health screening and interventions into the clinical management of patients with CKD.</p>
7 Authors
- Chang Seong Kim
- Sungyeon Kim
- Yeeun Lee
- Miseon Lee
- Hyeok Kang
- Seungyoon Nam
- Soo Wan Kim
2 Applications
| Application ID | Title |
|---|---|
| 82104 | Identification of biomarkers of chronic diseases using epidemiological and genomic information from the UK Biobank |
| 870121 | Discovery of biomarkers and development of treatment technology for kidney disease using epidemiological and genomic information from the UK Biobank |
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