TMEM14A Gene Affects Hippocampal Sclerosis in Mesial Temporal Lobe Epilepsy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects
2.2. Study Approval
2.3. Genotyping and Quality Control of SNPs
2.4. Genome-Wide Association Study
2.5. Allele Frequency in Normal Population
2.6. Genetic Correlation Analysis
2.7. Phenome-Wide Association Study
2.8. Quantitative Trait Locus Analyses
2.9. TMEM14A Expression Across Bulk Tissues
2.10. Transcriptomic Analysis in MTLE with HS
2.11. Transcriptomic Analysis in an Epilepsy Mouse Model
2.12. Prediction of Human and Mouse Phenotypes
2.13. Data Availability
3. Results
3.1. Genome-Wide Association Study
3.2. Phenome-Wide Association Study
3.3. Comparative Genetic Architecture Across Ancestries and Subtypes
3.4. Quantitative Trait Locus Analysis for rs6924849
3.5. Transcriptomic Investigation for TMEM14A
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
HS | hippocampal sclerosis |
SNPs | single-nucleotide polymorphisms |
MTLE | mesial temporal lobe epilepsy |
sQTL | splicing quantitative trait loci |
eQTL | expression quantitative trait loci |
GTEx | Genotype-Tissue Expression |
NES | normalized effect size |
LD | linkage disequilibrium |
EAS | East Asian |
EUR | European |
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HS Group (N = 52) | Non-HS Group (N = 105) | p-Value | |
---|---|---|---|
Age, years, mean ± SD | 36.5 ± 9.9 | 35.4 ± 10.7 | 0.496 |
Sex, female percentage | 51.9 | 45.7 | 0.573 |
Etiology, n (%) | - | - | <0.001 |
Symptomatic | 52 (100.0) | 45 (42.9) | - |
Cryptogenic | 0 (0.0) | 60 (57.1) | - |
Seizure type, n (%) | - | - | - |
Focal seizure with awareness | 1 (1.9) | 44 (41.9) | <0.001 |
Focal seizure with impaired awareness | 52 (100.0) | 76 (72.4) | <0.001 |
Focal to bilateral tonic–clonic | 6 (11.5) | 44 (41.9) | <0.001 |
Epileptogenic zone, n (%) | |||
Frontal | 0 (0.0) | 30 (28.6) | - |
Temporal | 52 (100.0) | 37 (35.2) | - |
Parietal | 0 (0.0) | 8 (7.6) | - |
Occipital | 0 (0.0) | 6 (5.7) | - |
Unknown | 0 (0.0) | 24 (22.9) | - |
SNP | Chr | Position GRCh37 | Position GRCh38 | Nearest Gene | Region | MAF | Alleles (Major/ Minor) | OR (95% CI) | p-Value | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Case | Control | Korea | Japan | Europe | |||||||||
rs1436751 | 1 | 65064340 | 64598657 | CACHD1 | intron | 0.44 | 0.2048 | 0.2611 | 0.1996 | 0.2684 | A/G | 3.194 (1.812, 5.63) | 0.000059 |
rs452930 | 6 | 94922837 | 94213119 | 0.5577 | 0.3317 | 0.4273 | 0.4113 | 0.3191 | C/T | 3.735 (1.962, 7.109) | 0.000059 | ||
rs11696024 | 2 | 19812104 | 19612343 | 0.3942 | 0.1810 | 0.2867 | 0.2784 | 0.8340 | G/A | 3.473 (1.889, 6.384) | 0.000061 | ||
rs6924849 | 6 | 52567028 | 52702230 | TMEM14A | downstream | 0.4423 | 0.1857 | 0.1938 | 0.1923 | 0.0467 | T/C | 2.685 (1.656, 4.353) | 0.000061 |
rs17219864 | 7 | 20773567 | 20733944 | ABCB5 | intron | 0.3558 | 0.1619 | 0.1983 | 0.1768 | 0.3529 | G/T | 3.549 (1.878, 6.708) | 0.000096 |
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Share and Cite
Kim, J.; Cho, S.; Jeong, K.H.; Ha, W.-S.; Kim, K.M.; Chu, M.K.; Lee, J.H.; Kim, S.; Kim, W.-J. TMEM14A Gene Affects Hippocampal Sclerosis in Mesial Temporal Lobe Epilepsy. J. Clin. Med. 2025, 14, 3810. https://doi.org/10.3390/jcm14113810
Kim J, Cho S, Jeong KH, Ha W-S, Kim KM, Chu MK, Lee JH, Kim S, Kim W-J. TMEM14A Gene Affects Hippocampal Sclerosis in Mesial Temporal Lobe Epilepsy. Journal of Clinical Medicine. 2025; 14(11):3810. https://doi.org/10.3390/jcm14113810
Chicago/Turabian StyleKim, Joonho, Soomi Cho, Kyoung Hoon Jeong, Woo-Seok Ha, Kyung Min Kim, Min Kyung Chu, Ji Hyun Lee, Sangwoo Kim, and Won-Joo Kim. 2025. "TMEM14A Gene Affects Hippocampal Sclerosis in Mesial Temporal Lobe Epilepsy" Journal of Clinical Medicine 14, no. 11: 3810. https://doi.org/10.3390/jcm14113810
APA StyleKim, J., Cho, S., Jeong, K. H., Ha, W.-S., Kim, K. M., Chu, M. K., Lee, J. H., Kim, S., & Kim, W.-J. (2025). TMEM14A Gene Affects Hippocampal Sclerosis in Mesial Temporal Lobe Epilepsy. Journal of Clinical Medicine, 14(11), 3810. https://doi.org/10.3390/jcm14113810