Exploring the association between familial hemiplegic migraine genes ( CACNA1A , ATP1A2 and SCN1A ) with migraine and epilepsy: A UK Biobank exome-wide association study
Abstract
Background Familial hemiplegic migraine (FHM) types 1–3 are associated with protein-altering genetic variants in CACNA1A, ATP1A2 and SCN1A, respectively. These genes have also been linked to epilepsy. Previous studies primarily focused on phenotypes, examining genetic variants in individuals with characteristic FHM symptoms. This study aimed to investigate the association of FHM genetic variation with migraine and epilepsy, utilizing a genotype-first approach. Methods Whole-exome sequence data from 454,706 individuals from the UK Biobank were examined for self-reported and inpatient-diagnosed migraine and epilepsy. Carriers were compared with non-carriers in a burden analysis using logistic regression while accounting for age, biological sex and UK Biobank assessment center. A machine learning-based approach was employed to predict whether variants resulted in gain-of-function (GoF), loss-of-function (LoF) or neutral effects. Results Heterozygous carriers of GoF CACNA1A variants, LoF ATP1A2 variants or neutral SCN1A variants were at increased risk of migraine. Homozygous carriers of neutral SCN1A variants were also associated with migraine but these carriers showed a reduced disease risk of epilepsy. Conclusions Heterozygous genotypes in all three FHM genes were associated with migraine but not epilepsy in this genotype-focused study. Homozygous SCN1A genotypes also showed increased disease risk of migraine, yet these carriers were protected against epilepsy.
Read the paper
Related studies
- Calcium Ions in the Physiology and Pathology of the Central Nervous System
- AI-powered in silico twins: redefining precision medicine through simulation, personalization, and predictive healthcare
- In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene
- In Silico drug repurposing pipeline using deep learning and structure based approaches in epilepsy
- Targeting serotonin receptors with phytochemicals – an in-silico study
- In silico exploration of anti-prostate cancer compounds from differential expressed genes
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.