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Dissecting the Shared Genetic Architecture of Common Epilepsies With Cortical Brain Morphology.
Karadag, Naz; Hagen, Espen; Shadrin, Alexey A; van der Meer, Dennis; O'Connell, Kevin S; Rahman, Zillur; Kutrolli, Gleda; Parker, Nadine; Bahrami, Shahram; Fominykh, Vera; Heuser, Kjell; Taubøll, Erik; Steen, Nils Eiel; Djurovic, Srdjan; Dale, Anders M; Frei, Oleksandr; Andreassen, Ole A; Smeland, Olav B.
Afiliación
  • Karadag N; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Hagen E; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Shadrin AA; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • van der Meer D; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • O'Connell KS; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Rahman Z; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Kutrolli G; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Parker N; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Bahrami S; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Fominykh V; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Heuser K; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Taubøll E; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Steen NE; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Djurovic S; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Dale AM; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Frei O; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Andreassen OA; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
  • Smeland OB; From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Facult
Neurol Genet ; 10(3): e200143, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38817246
ABSTRACT
Background and

Objectives:

Epilepsies are associated with differences in cortical thickness (TH) and surface area (SA). However, the mechanisms underlying these relationships remain elusive. We investigated the extent to which these phenotypes share genetic influences.

Methods:

We analyzed genome-wide association study data on common epilepsies (n = 69,995) and TH and SA (n = 32,877) using Gaussian mixture modeling MiXeR and conjunctional false discovery rate (conjFDR) analysis to quantify their shared genetic architecture and identify overlapping loci. We biologically interrogated the loci using a variety of resources and validated in independent samples.

Results:

The epilepsies (2.4 k-2.9 k variants) were more polygenic than both SA (1.8 k variants) and TH (1.3 k variants). Despite absent genome-wide genetic correlations, there was a substantial genetic overlap between SA and genetic generalized epilepsy (GGE) (1.1 k), all epilepsies (1.1 k), and juvenile myoclonic epilepsy (JME) (0.7 k), as well as between TH and GGE (0.8 k), all epilepsies (0.7 k), and JME (0.8 k), estimated with MiXeR. Furthermore, conjFDR analysis identified 15 GGE loci jointly associated with SA and 15 with TH, 3 loci shared between SA and childhood absence epilepsy, and 6 loci overlapping between SA and JME. 23 loci were novel for epilepsies and 11 for cortical morphology. We observed a high degree of sign concordance in the independent samples.

Discussion:

Our findings show extensive genetic overlap between generalized epilepsies and cortical morphology, indicating a complex genetic relationship with mixed-effect directions. The results suggest that shared genetic influences may contribute to cortical abnormalities in epilepsies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Neurol Genet Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Neurol Genet Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos