Correlation of polygenic risk score and clinical phenotype in patients with genetic generalized epilepsy
Abstract
Abstract Objective The polygenic risk score (PRS) for individuals with genetic generalized epilepsy (GGE) quantifies the common risk variants in genes identified in genome‐wide association studies. We hypothesized that the phenotype of GGE patients differs based on their GGE PRS. Methods We identified participants with highest ( n = 59) versus lowest ( n = 48) PRS from the GGE patients ( n = 2256) recruited through the Epi25 Collaborative for comparison. Detailed clinical data were acquired retrospectively for the 59 high PRS and 48 low PRS individuals with GGE from the Epi25 database and from the contributing centers. For validation, we accessed a larger cohort ( n = 1175) of patients with GGE included in the Epi25 Collaborative. Results This study found no difference in phenotypic features of patients between the high‐PRS GGE and low‐PRS GGE subgroups, including age at onset, family history, and specific GGE syndrome. However, more patients from the lowest compared to the highest PRS subgroup were pharmacoresistant (31.7% vs. 8.9%, p = .01). On validation in a larger cohort, the PRS did not differ in the group of pharmacoresistant compared to nonpharmacoresistant patients. Significance No meaningful association between PRS and age at onset, history of febrile seizures, pre‐/perinatal complications, epilepsy syndromes, seizure types, co‐occurrence of functional/dissociative (nonepileptic) seizures, psychiatric comorbidities, electroencephalographic/magnetic resonance imaging findings, or drug response could be demonstrated in this study of people with GGE.
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Authors: Sophie von Brauchitsch, Nils Hartung, Robin A. Karge, Bobby Koeleman, Samuel F. Berkovic, Danielle M. Andrade, Francesca Bisulli, Antonio Gambardella, Renzo Guerrini, Ingrid E. Scheffer, Ingo Helbig, Wolfram S. Kunz, Holger Lerche, Hiltrud Muhle, Christian M. Boßelmann, Savvas S. Papacostas, Mark I. Rees, Sanjay M. Sisodiya, Pasquale Striano, Lynette G. Sadleir, Yvonne Weber, Dennis Lal, Costin Leu, Philipp S. Reif, Stefan Wolking, Felix Rosenow, Karl Martin Klein, for the Epi25 Collaborative
Institutions: The University of Melbourne, Children's Hospital of Philadelphia, University of Cologne, University College London, University of Otago, University of Bologna, RWTH Aachen University, University of Bonn, Goethe University Frankfurt, Epilepsy Research UK, Broad Institute, Alberta Children's Hospital, Florey Institute of Neuroscience and Mental Health, Murdoch Children's Research Institute, Austin Health, Magna Graecia University, Swansea University, Meyer Children's Hospital, University of Genoa, The University of Texas Health Science Center, Utrecht University, Cleveland Clinic, University Medical Center Utrecht, Ontario Brain Institute, Istituto Giannina Gaslini, Cleveland Clinic Lerner College of Medicine, University Hospital Bonn, Christian-Albrechts-Universität zu Kiel, Hertie Institute for Clinical Brain Research, Istituto delle Scienze Neurologiche di Bologna, Cyprus Institute of Neurology and Genetics, Epilepsy Society