A Polygenic Resilience Score Moderates the Genetic Risk for Schizophrenia: Replication in 18,090 Cases and 28,114 Controls from the Psychiatric Genomics Consortium

Identifying heritable factors that moderate the genetic risk for schizophrenia (SCZ) could help clarify why some individuals remain unaffected despite having relatively high genetic liability. Previously, we developed a framework to mine genome-wide association (GWAS) data for common genetic variant...

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Detalles Bibliográficos
Autores: Hess, Jonathan, Mattheisen, Manuel, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Greenwood, Tiffany A., Tsuang, Ming T, Edenberg, Howard J., Holmans, Peter, Faraone, Stephen V., Glatt, Stephen J., Fañanas Saura, Lourdes
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/227934
Acceso en línea:https://hdl.handle.net/2445/227934
Access Level:acceso abierto
Palabra clave:Escales d'avaluació psiquiàtrica
Epidemiologia genètica
Esquizofrènia
Psychiatric rating scales
Genetic epidemiology
Schizophrenia
Descripción
Sumario:Identifying heritable factors that moderate the genetic risk for schizophrenia (SCZ) could help clarify why some individuals remain unaffected despite having relatively high genetic liability. Previously, we developed a framework to mine genome-wide association (GWAS) data for common genetic variants that protect high-risk unaffected individuals from SCZ, leading to derivation of the first-ever "polygenic resilience score" for SCZ (resilient controls n = 3786; polygenic risk score-matched SCZ cases n = 18,619). Here, we performed a replication study to verify the moderating effect of our polygenic resilience score on SCZ risk (OR = 1.09, p = 4.03 × 10-5 ) using newly released GWAS data from 23 independent case-control studies collated by the Psychiatric Genomics Consortium (PGC) (resilient controls n = 2821; polygenic risk score-matched SCZ cases n = 5150). Additionally, we sought to optimize our polygenic resilience-scoring formula to improve subsequent modeling of resilience to SCZ and other complex disorders. We found significant replication of the polygenic resilience score, and found that strict pruning of SNPs based on linkage disequilibrium to known risk SNPs and their linked loci optimizes the performance of the polygenic resilience score.

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