Leu, Costin, Richardson, Tom G., Kaufmann, Tobias ORCID: 0000-0002-4003-1018, van der Meer, Dennis ORCID: 0000-0002-0466-386X, Andreassen, Ole A., Westlye, Lars T. ORCID: 0000-0001-8644-956X, Busch, Robyn M., Smith, George Davey ORCID: 0000-0002-1407-8314 and Lal, Dennis (2020). Pleiotropy of polygenic factors associated with focal and generalized epilepsy in the general population. PLoS One, 15 (4). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Epilepsy is clinically heterogeneous, and neurological or psychiatric comorbidities are frequently observed in patients. It has not been tested whether common risk variants for generalized or focal epilepsy are enriched in people with other disorders or traits related to brain or cognitive function. Here, we perform two brain-focused phenome association studies of polygenic risk scores (PRS) for generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) with all binary brain or cognitive function-related traits available for 334,310 European-ancestry individuals of the UK Biobank. Higher GE-PRS were associated with not having a college or university degree (P = 3.00x10(-4)), five neuroticism-related personality traits (P<2.51x10(-4)), and having ever smoked (P = 1.27x10(-6)). Higher FE-PRS were associated with several measures of low educational attainment (P<4.87x10(-5)), one neuroticism-related personality trait (P = 2.33x10(-4)), having ever smoked (P = 1.71x10(-4)), and having experienced events of anxiety or depression (P = 2.83x10(-4)). GE- and FE-PRS had the same direction of effect for each of the associated traits. Genetic factors associated with GE or FE showed similar patterns of correlation with genetic factors associated with cortical morphology in a subset of the UKB with 16,612 individuals and T1 magnetic resonance imaging data. In summary, our results suggest that genetic factors associated with epilepsies may confer risk for other neurological and psychiatric disorders in a population sample not enriched for epilepsy.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Leu, CostinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Richardson, Tom G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaufmann, TobiasUNSPECIFIEDorcid.org/0000-0002-4003-1018UNSPECIFIED
van der Meer, DennisUNSPECIFIEDorcid.org/0000-0002-0466-386XUNSPECIFIED
Andreassen, Ole A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Westlye, Lars T.UNSPECIFIEDorcid.org/0000-0001-8644-956XUNSPECIFIED
Busch, Robyn M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smith, George DaveyUNSPECIFIEDorcid.org/0000-0002-1407-8314UNSPECIFIED
Lal, DennisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-336235
DOI: 10.1371/journal.pone.0232292
Journal or Publication Title: PLoS One
Volume: 15
Number: 4
Date: 2020
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ACCURACY; HEALTHMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33623

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