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Aim: Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE). Materials & methods: We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE – responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid. Results: Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10-5) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment. Conclusion: This first GWAS of AED response in GGE provides a comprehensive reference of SNP associations for hypothesis-driven candidate gene analyses in upcoming pharmacogenetic studies.
Background and purpose: The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain. Methods: We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders. We describe how we have tackled methodological issues surrounding genetic meta-analysis of EEG features. We discuss the importance of harmonizing EEG signal processing, cleaning, and feature extraction. Finally, we explain our selection of EEG features currently being investigated, including the temporal dynamics of oscillations and the connectivity network based on synchronization of oscillations. Results: We present data that show how to perform systematic quality control and evaluate how choices in reference electrode and montage affect individual differences in EEG parameters. Conclusion: The long list of potential challenges to our large-scale meta-analytic approach requires extensive effort and organization between participating cohorts; however, our perspective shows that these challenges are surmountable. Our perspective argues that elucidating the genetic of EEG oscillatory activity is a worthwhile effort in order to elucidate the pathway from gene to disease liability.
Auch Sarah Sander befasst sich in ihrem Beitrag mit der politischen Dimension des Kuratierens, die sie durch die Untersuchung der künstlerischen Strategie des Arrangements in der Arbeit von Forensic Architecture und bei Guillermo Galindo herausstellt. Beide, Künstler wie Kollektiv, arbeiten mit vorgefundenen Materialen und Bildern, die neu arrangiert werden, um "den massenmedialen Bildern und Diskursen etwas entgegenzustellen" (Sander). Jedoch verfolgt das Arrangieren jeweils unterschiedliche politische Ziele: Während das Forensic Architecture Kollektiv mit seinen Arbeiten Sichtbarkeit und Nachvollziehbarkeit erzeugt, geht es Galindo vielmehr darum, Hörbarkeit herzustellen; in ihrem Widerstand gegen fortwirkende rassistische Strukturen schreibe sich beide in eine Praxis ein, die Sander mit Christina Sharpe als 'wake work' beschreibt.