Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies

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dc.contributor.author Int League Against Epilepsy Conso
dc.contributor.author Abou-Khalil, Bassel
dc.contributor.author Eriksson, Johan G.
dc.contributor.author Lehesjoki, Anna-Elina
dc.contributor.author Palotie, Aarno
dc.date.accessioned 2019-01-07T15:03:02Z
dc.date.available 2019-01-07T15:03:02Z
dc.date.issued 2018-12-10
dc.identifier.citation Int League Against Epilepsy Conso , Abou-Khalil , B , Eriksson , J G , Lehesjoki , A-E & Palotie , A 2018 , ' Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies ' , Nature Communications , vol. 9 , 5269 . https://doi.org/10.1038/s41467-018-07524-z
dc.identifier.other PURE: 120808761
dc.identifier.other PURE UUID: 00856f27-7109-4b84-af35-18f32d7f63ba
dc.identifier.other WOS: 000452633700009
dc.identifier.other Scopus: 85058169154
dc.identifier.other ORCID: /0000-0002-2527-5874/work/97266470
dc.identifier.uri http://hdl.handle.net/10138/287694
dc.description.abstract The epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report a genome-wide mega-analysis involving 15,212 individuals with epilepsy and 29,677 controls, which reveals 16 genome-wide significant loci, of which 11 are novel. Using various prioritization criteria, we pinpoint the 21 most likely epilepsy genes at these loci, with the majority in genetic generalized epilepsies. These genes have diverse biological functions, including coding for ion-channel subunits, transcription factors and a vitamin-B6 metabolism enzyme. Converging evidence shows that the common variants associated with epilepsy play a role in epigenetic regulation of gene expression in the brain. The results show an enrichment for monogenic epilepsy genes as well as known targets of antiepileptic drugs. Using SNP-based heritability analyses we disentangle both the unique and overlapping genetic basis to seven different epilepsy subtypes. Together, these findings provide leads for epilepsy therapies based on underlying pathophysiology. en
dc.format.extent 15
dc.language.iso eng
dc.relation.ispartof Nature Communications
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject LD SCORE REGRESSION
dc.subject SUSCEPTIBILITY LOCI
dc.subject GENETIC ARCHITECTURE
dc.subject SNP HERITABILITY
dc.subject ILAE COMMISSION
dc.subject FRONTAL-LOBE
dc.subject ASSOCIATION
dc.subject METAANALYSIS
dc.subject EXPRESSION
dc.subject ABSENCE
dc.subject 3111 Biomedicine
dc.title Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies en
dc.type Article
dc.contributor.organization Johan Eriksson / Principal Investigator
dc.contributor.organization Department of General Practice and Primary Health Care
dc.contributor.organization Clinicum
dc.contributor.organization Department of Medical and Clinical Genetics
dc.contributor.organization Medicum
dc.contributor.organization Centre of Excellence in Complex Disease Genetics
dc.contributor.organization Aarno Palotie / Principal Investigator
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Genomics of Neurological and Neuropsychiatric Disorders
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/s41467-018-07524-z
dc.relation.issn 2041-1723
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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