Badanie asocjacyjne całego genotypu na dużą skalę zidentyfikowało wspólne genetyczne warianty ryzyka w epilepsji i chorobie Alzheimera
Large-Scale Genome-wide association study identified Shared Genetic Risk SNPs Correlates in Epilepsy and Alzheimer's Disease
W skrócie
[Preprint - wstępne wyniki] Naukowcy zbadali związek między epilepsją a chorobą Alzheimera, analizując dane genetyczne ponad 800 pacjentów z epilepsją i 39 tysięcy osób z Alzheimerem. Wyniki sugerują, że epilepsja może zwiększać ryzyko rozwoju Alzheimera, a naukowcy zidentyfikowali konkretny wariant genetyczny (rs429358), który może być wspólny dla obu chorób. Badacze podkreślają, że wyniki są wstępne i wymagają potwierdzenia w większych grupach pacjentów.
Oryginalny abstract (angielski)
Abstract Background: The etiology of Alzheimer’s disease (AD) is an intricate pathological mechanism. Increasing evidence has demonstrated a significant association between epilepsy and the development or progression of Alzheimer's disease. Methods: Two-sample MR evaluated focal epilepsy with documented hippocampal sclerosis as the exposure and AD as the outcome. The epilepsy dataset included 803 cases and 29,677 controls, while the AD dataset comprised 39,106 clinically diagnosed cases, 46,828 proxy cases, and 401,577 controls. After linkage disequilibrium clumping, harmonization, instrument-strength assessment, and Steiger filtering, two independent variants were retained. Additional UK Biobank association analyses were performed using REGENIE, including 57,795 AD cases with approximately 283,500 controls and 4,556 epilepsy cases with 289,065 controls. Associated loci were characterized using FUMA, MAGMA, regulatory annotation, and Bayesian colocalization. Results: Inverse-variance weighted MR indicated that genetically predicted focal epilepsy with hippocampal sclerosis was associated with increased odds of AD (OR=3.99, 95% CI 1.17–13.61; P=0.027). No heterogeneity was detected (Cochran’s Q=0.006, P=0.939; I²=0%). In the UK Biobank epilepsy GWAS, 95 variants reached the suggestive threshold (P Conclusion: Using large-scale datasets, including UK Biobank and IEU data, these findings provide preliminary evidence that epilepsy may increase AD susceptibility and identify rs429358 as a potential overlap SNP with shared potential biological signal pathways. Larger epilepsy datasets and independent replication are required.