Gene-Burden Meta-Analysis of 748,879 Individuals Identifies LGI1-ADAM23 Protein Complex Association with Epilepsy
Abstract number :
1.094
Submission category :
12. Genetics / 12A. Human Studies
Year :
2025
Submission ID :
881
Source :
www.aesnet.org
Presentation date :
12/6/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Costin Leu, PhD – McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Jessica Lal, PhD – University of Texas
Christian Bosselmann, MD – Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany
Alina Ivaniuk, MD, PhD – Mayo Clinic in Florida
Eduardo Pérez-Palma, PhD – Facultad de Medicina Clínica Alemana
Dennis Lal, PhD – Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Rationale: Epilepsy affects over 50 million individuals globally and has a substantial genetic component that remains to be completely understood. Traditional studies have focused on severe, early-onset cases enrolled through clinical or research settings. Recent biobank-based approaches, leveraging large-scale population datasets, offer opportunities to explore genetic associations in broader epilepsy/seizure phenotypes, including milder, later-onset forms.
Methods: We re-evaluated gene-based rare variant association statistics from the Broad CVDI Human Disease Portal in 20,026 individuals with epilepsy compared to 728,853 population controls from the UK Biobank, All of Us, and the Massachusetts General Brigham Biobank. The only epilepsy-related phecode that was mappable across all three studies was #345 “Epilepsy, recurrent seizures, convulsions”. Rare variants were filtered and tested using six masks, including different combinations of loss-of-function (LoF) variants and deleterious missense variants, at three maximum frequency filters across all collapsed variants in each gene (maximum combined minor allele frequencies (AF) of all tested variants in each gene < 1%, < 0.1%, and < 0.001%).
Genetics