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

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http://hdl.handle.net/10138/287694

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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

Titel: Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies
Författare: Int League Against Epilepsy Conso; Abou-Khalil, Bassel; Eriksson, Johan G.; Lehesjoki, Anna-Elina; Palotie, Aarno
Upphovmannens organisation: Johan Eriksson / Principal Investigator
Department of General Practice and Primary Health Care
Clinicum
Department of Medical and Clinical Genetics
Medicum
Centre of Excellence in Complex Disease Genetics
Aarno Palotie / Principal Investigator
Institute for Molecular Medicine Finland
Genomics of Neurological and Neuropsychiatric Disorders
Datum: 2018-12-10
Språk: eng
Sidantal: 15
Tillhör serie: Nature Communications
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-018-07524-z
Permanenta länken (URI): http://hdl.handle.net/10138/287694
Abstrakt: 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.
Subject: LD SCORE REGRESSION
SUSCEPTIBILITY LOCI
GENETIC ARCHITECTURE
SNP HERITABILITY
ILAE COMMISSION
FRONTAL-LOBE
ASSOCIATION
METAANALYSIS
EXPRESSION
ABSENCE
3111 Biomedicine
Referentgranskad: Ja
Licens: cc_by
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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