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GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

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dc.contributor.authorTÜRKDOĞAN, DİLŞAD
dc.contributor.authorsStevelink R., Campbell C., Chen S., Abou-Khalil B., Adesoji O. M., Afawi Z., Amadori E., Anderson A., Anderson J., Andrade D. M., et al.
dc.date.accessioned2023-09-12T05:32:09Z
dc.date.available2023-09-12T05:32:09Z
dc.date.issued2023-01-01
dc.description.abstractEpilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment.
dc.identifier.citationStevelink R., Campbell C., Chen S., Abou-Khalil B., Adesoji O. M., Afawi Z., Amadori E., Anderson A., Anderson J., Andrade D. M., et al., "GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture", Nature Genetics, 2023
dc.identifier.doi10.1038/s41588-023-01485-w
dc.identifier.issn1061-4036
dc.identifier.urihttps://avesis.marmara.edu.tr/api/publication/0f124b0b-5c0f-476f-ad34-513cfd6322b8/file
dc.identifier.urihttps://hdl.handle.net/11424/293158
dc.language.isoeng
dc.relation.ispartofNature Genetics
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectTıp
dc.subjectDahili Tıp Bilimleri
dc.subjectTıbbi Genetik
dc.subjectYaşam Bilimleri
dc.subjectMoleküler Biyoloji ve Genetik
dc.subjectSağlık Bilimleri
dc.subjectTemel Bilimler
dc.subjectMedicine
dc.subjectInternal Medicine Sciences
dc.subjectMedical Genetics
dc.subjectLife Sciences
dc.subjectMolecular Biology and Genetics
dc.subjectHealth Sciences
dc.subjectNatural Sciences
dc.subjectYaşam Bilimleri (LIFE)
dc.subjectGENETİK VE KALITIM
dc.subjectLife Sciences (LIFE)
dc.subjectMOLECULAR BIOLOGY & GENETICS
dc.subjectGENETICS & HEREDITY
dc.subjectGenetik
dc.subjectGenetics
dc.titleGWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture
dc.typearticle
dspace.entity.typePublication
local.avesis.id0f124b0b-5c0f-476f-ad34-513cfd6322b8
local.indexed.atPUBMED
local.indexed.atSCOPUS
relation.isAuthorOfPublication0a1599c4-48ff-4aa9-b689-3927c986a650
relation.isAuthorOfPublication.latestForDiscovery0a1599c4-48ff-4aa9-b689-3927c986a650

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