Evidence map›Paper›PMID 39388989›Full record

ArticleSeizure2024

Unraveling the shared genetics of common epilepsies and general cognitive ability.

Naz Karadag, Espen Hagen, Alexey A Shadrin, Dennis van der Meer, Kevin S O'Connell, Zillur Rahman, Gleda Kutrolli, Nadine Parker, Shahram Bahrami, Vera Fominykh and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Seizure, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Naz KaradagCentre for Precision Psychiatry, University of Oslo, Oslo, Norway. Electronic address: naz.karadag@medisin.uio.no.
Espen HagenCentre for Precision Psychiatry, University of Oslo, Oslo, Norway. Electronic address: espen.hagen@medisin.uio.no.
Alexey A ShadrinCentre for Precision Psychiatry, University of Oslo, Oslo, Norway; K.G. Jebsen Centre for Neurodevelopmental disorders, University of Oslo and Oslo University Hospital, Oslo, Norway. Electronic address: alexey.shadrin@medisin.uio.no.
Dennis van der MeerCentre for Precision Psychiatry, University of Oslo, Oslo, Norway; School of Mental Health and Neuroscience, Faculty of Health, Maastricht University, Maastricht, Netherlands. Electronic address: d.van.der.meer@medisin.uio.no.
Kevin S O'ConnellCentre for Precision Psychiatry, University of Oslo, Oslo, Norway. Electronic address: k.s.oconnell@medisin.uio.no.
Zillur RahmanDivision of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. Electronic address: zillurbmb51@gmail.com.
Gleda KutrolliCentre for Precision Psychiatry, University of Oslo, Oslo, Norway. Electronic address: gleda.kutrolli@medisin.uio.no.
Nadine ParkerCentre for Precision Psychiatry, University of Oslo, Oslo, Norway. Electronic address: nadine.parker@medisin.uio.no.
Shahram BahramiCentre for Precision Psychiatry, University of Oslo, Oslo, Norway. Electronic address: shahram.bahrami@medisin.uio.no.
Vera FominykhCentre for Precision Psychiatry, University of Oslo, Oslo, Norway. Electronic address: vera.fominykh@medisin.uio.no.
Kjell HeuserDepartment of Neurology, Oslo University Hospital, Oslo, Norway. Electronic address: kheuser@ous-hf.no.
Erik TaubøllDepartment of Neurology, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: erik.tauboll@medisin.uio.no.
Torill UelandDivision of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway. Electronic address: torill.ueland@psykologi.uio.no.
Nils Eiel SteenCentre for Precision Psychiatry, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway. Electronic address: n.e.steen@medisin.uio.no.
Srdjan DjurovicDepartment of Medical Genetics, Oslo University Hospital, Oslo, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway. Electronic address: srdjan.djurovic@medisin.uio.no.
Anders M DaleDepartment of Cognitive Science, University of California, San Diego, United States; Multimodal Imaging Laboratory, University of California, San Diego, United States; Department of Psychiatry, University of California, San Diego, United States; Department of Neurosciences, University of California, San Diego, United States. Electronic address: andersmdale@gmail.com.
Oleksandr FreiCentre for Precision Psychiatry, University of Oslo, Oslo, Norway; Center for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway. Electronic address: oleksandr.frei@medisin.uio.no.
Ole A AndreassenCentre for Precision Psychiatry, University of Oslo, Oslo, Norway; K.G. Jebsen Centre for Neurodevelopmental disorders, University of Oslo and Oslo University Hospital, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. Electronic address: ole.andreassen@medisin.uio.no.
Olav B SmelandCentre for Precision Psychiatry, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. Electronic address: o.b.smeland@medisin.uio.no.

Funding

OTA-21-015A Post-Acute Sequelae of SARS-CoV-2 Infection Initiative: NYU Langone Health Clinical Science Core, Data Resource Core, and PASC Biorepository CoreOT2HL161847 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI GROSS, RACHEL SHARON, HORWITZ, LEORA · 2021 to 2025
$651.0M
ABCD-USA Consortium: Data Analysis, Informatics and Resource CenterU24DA041123 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ANDERS M DALE · 2015 to 2026
$51.5M
Healthy Brain and Child Development National Consortium Data Coordinating CenterU24DA055330 · NIDA · WASHINGTON UNIVERSITY · PI ANDERS M DALE, Damien A Fair · 2021 to 2026
$34.6M
The VETSA Longitudinal MRI Twin Study of Aging (VETSA MRI 4)R01AG076838 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ANDERS M DALE, Jeremy A Elman · 2022 to 2026
$8.7M
A Trans-Nordic Study of Extreme Major DepressionR01MH123724 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PATRICK F SULLIVAN, Lu Yi · 2020 to 2026
$4.7M
3/7 Psychiatric Genomics Consortium: Advancing Discovery and ImpactR01MH124839 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ANDREASSEN, OLE A, HUCKINS, LAURA MARIANNE · 2021 to 2025
$2.0M
NHLBI NIH HHS OT2 HL161847NIA NIH HHS R01 AG076838NIDA NIH HHS U24 DA041123NIDA NIH HHS U24 DA055330NIMH NIH HHS R01 MH123724NIMH NIH HHS R01 MH124839
6 · The paper itself

Abstract

purposeCognitive impairment is prevalent among individuals with epilepsy, and increasing evidence indicates that genetic factors can underlie this relationship. However, the extent to which epilepsy subtypes differ in their genetic relationship with cognitive function, and information about the specific genetic variants involved remain largely unknown.

methodsWe investigated the genetic relationship between epilepsies and general cognitive ability (COG) using complementary statistical tools, including linkage disequilibrium score (LDSC) regression, MiXeR and conjunctional false discovery rate (conjFDR). We analyzed genome-wide association study data on COG (n = 269,867) and common epilepsies (n = 27,559 cases, 42,436 controls), including the broad phenotypes 'all epilepsy', focal epilepsies and genetic generalized epilepsies (GGE), as well as specific subtypes. We functionally annotated the identified loci using several biological resources and validated the results in independent samples.

resultsUsing MiXeR, COG (11.2k variants) was estimated to be almost four times more polygenic than 'all epilepsy', GGE, juvenile myoclonic epilepsy (JME), and childhood absence epilepsy (CAE) (2.5k - 2.9k variants). The other epilepsy phenotypes were insufficiently powered for MiXeR analysis. We quantified extensive genetic overlap between COG and epilepsy types, but with varying negative genetic correlations (-0.23 to -0.04). COG was estimated to share 2.9k variants with both GGE and 'all epilepsy', and 2.3k variants with both JME and CAE. Using conjFDR, we identified 66 distinct loci shared between COG and epilepsies, including novel associations for GGE (27), 'all epilepsy' (5), JME (5) and CAE (5). The implicated genes were significantly expressed in multiple brain regions. The results were validated in independent samples (COG: p = 3.62 × 10

conclusionOur study further dissects the substantial genetic basis shared between epilepsies and COG and identifies novel shared loci. An improved understanding of the genetic relationship between epilepsies and COG may lead to the development of novel comorbidity-targeted epilepsy treatments.

Indexed as

EpilepsyGenome-Wide Association StudyCognitionCognitive DysfunctionFemaleHumansLinkage DisequilibriumMalePhenotypePolymorphism, Single NucleotideCognitionConjFDRConjunctional False Discovery RateEpilepsyGaussian causal mixture modelsLDSCLinkage disequilibrium score regressionMiXeRPolygenic overlap

Identifiers

PMID39388989
PMCPMC11681332

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.