Universität zu Köln

Gramm, Marie, Leu, Costin, Perez-Palma, Eduardo, Ferguson, Lisa, Jehi, Lara ORCID: 0000-0002-8041-6377, Daly, Mark J., Najm, Imad M., Busch, Robyn M. and Lal, Dennis (2020). Polygenic risk heterogeneity among focal epilepsies. Epilepsia, 61 (11). S. E179 - 7. HOBOKEN: WILEY. ISSN 1528-1167

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Abstract

Focal epilepsy (FE) is clinically highly heterogeneous. It has been shown recently that not only rare but also a subset of common genetic variants confer risk for FE. The relatively modest power of genetic studies in FE suggests a high genetic heterogeneity of FE when grouped as one disorder. We hypothesize that the clinical heterogeneity of FE is correlated with genetic heterogeneity on a common risk variant level. To test the hypothesis, we used an FE polygenic risk score FE-PRS that combines small effect sizes of thousands of common variants from the largest FE-GWAS (genome-wide association study) into a single measure. We grouped 414 individuals with FE according to common clinical features into subgroups, either by one feature at a time or by all features combined in a cluster analysis. We examined their association with FE-PRS compared to 20 435 matched population controls and observed heterogeneous FE-PRS burden among the subgroups. The highest phenotypic variance explained by FE-PRS was identified in a cluster analysis-defined FE subgroup where all individuals had unknown etiologies and psychiatric comorbidities, and the majority had early onset seizures. Our results indicate that genetic factors associated with FE have differential burden among FE subtypes. Future studies using better-powered FE-PRS might have clinical utility.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gramm, Marie UNSPECIFIED UNSPECIFIED UNSPECIFIED Leu, Costin UNSPECIFIED UNSPECIFIED UNSPECIFIED Perez-Palma, Eduardo UNSPECIFIED UNSPECIFIED UNSPECIFIED Ferguson, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Jehi, Lara UNSPECIFIED orcid.org/0000-0002-8041-6377 UNSPECIFIED Daly, Mark J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Najm, Imad M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Busch, Robyn M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lal, Dennis UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-315045
DOI:	10.1111/epi.16717
Journal or Publication Title:	Epilepsia
Volume:	61
Number:	11
Page Range:	S. E179 - 7
Date:	2020
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1528-1167
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COMMON GENETIC-VARIATION; SUSCEPTIBILITY; METAANALYSIS; SEIZURES Multiple languages Clinical Neurology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31504