Articles producció científica> Medicina i Cirurgia

Common genetic variants contribute to heritability of age at onset of schizophrenia

  • Identification data

    Identifier: imarina:9321839
    Authors:
    Sada-Fuente, EAranda, SPapiol, SHeilbronner, UMoltó, MDAguilar, EJGonzález-Peñas, JAndreu-Bernabeu, AArango, CCrespo-Facorro, BGonzález-Pinto, AFañanás, LArias, BBobes, JCostas, JMartorell, LSchulze, TGKalman, JLVilella, EMuntané, G
    Abstract:
    Schizophrenia (SCZ) is a complex disorder that typically arises in late adolescence or early adulthood. Age at onset (AAO) of SCZ is associated with long-term outcomes of the disease. We explored the genetic architecture of AAO with a genome-wide association study (GWAS), heritability, polygenic risk score (PRS), and copy number variant (CNV) analyses in 4 740 subjects of European ancestry. Although no genome-wide significant locus was identified, SNP-based heritability of AAO was estimated to be between 17 and 21%, indicating a moderate contribution of common variants. We also performed cross-trait PRS analyses with a set of mental disorders and identified a negative association between AAO and common variants for SCZ, childhood maltreatment and attention-deficit/hyperactivity disorder. We also investigated the role of copy number variants (CNVs) in AAO and found an association with the length and number of deletions (P-value = 0.03), whereas the presence of CNVs previously reported in SCZ was not associated with earlier onset. To our knowledge, this is the largest GWAS of AAO of SCZ to date in individuals from European ancestry, and the first study to determine the involvement of common variants in the heritability of AAO. Finally, we evidenced the role played by higher SCZ load in determining AAO but discarded the role of pathogenic CNVs. Altogether, these results shed light on the genetic architecture of AAO, which needs to be confirmed with larger studies.© 2023. The Author(s).
  • Others:

    Author, as appears in the article.: Sada-Fuente, E; Aranda, S; Papiol, S; Heilbronner, U; Moltó, MD; Aguilar, EJ; González-Peñas, J; Andreu-Bernabeu, A; Arango, C; Crespo-Facorro, B; González-Pinto, A; Fañanás, L; Arias, B; Bobes, J; Costas, J; Martorell, L; Schulze, TG; Kalman, JL; Vilella, E; Muntané, G
    Department: Medicina i Cirurgia
    URV's Author/s: Aranda Castel, Selena / Martorell Bonet, Lourdes / Muntané Medina, Gerard / Sada Fuente, Ester / Vilella Cuadrada, Elisabet
    Keywords: Genome-wide association sex-differences risk psychosis of-onset metaanalysis copy number variants
    Abstract: Schizophrenia (SCZ) is a complex disorder that typically arises in late adolescence or early adulthood. Age at onset (AAO) of SCZ is associated with long-term outcomes of the disease. We explored the genetic architecture of AAO with a genome-wide association study (GWAS), heritability, polygenic risk score (PRS), and copy number variant (CNV) analyses in 4 740 subjects of European ancestry. Although no genome-wide significant locus was identified, SNP-based heritability of AAO was estimated to be between 17 and 21%, indicating a moderate contribution of common variants. We also performed cross-trait PRS analyses with a set of mental disorders and identified a negative association between AAO and common variants for SCZ, childhood maltreatment and attention-deficit/hyperactivity disorder. We also investigated the role of copy number variants (CNVs) in AAO and found an association with the length and number of deletions (P-value = 0.03), whereas the presence of CNVs previously reported in SCZ was not associated with earlier onset. To our knowledge, this is the largest GWAS of AAO of SCZ to date in individuals from European ancestry, and the first study to determine the involvement of common variants in the heritability of AAO. Finally, we evidenced the role played by higher SCZ load in determining AAO but discarded the role of pathogenic CNVs. Altogether, these results shed light on the genetic architecture of AAO, which needs to be confirmed with larger studies.© 2023. The Author(s).
    Thematic Areas: Saúde coletiva Psychiatry and mental health Psychiatry Psicología Nutrição Medicina ii Medicina i Linguística e literatura Interdisciplinar Engenharias iv Enfermagem Educação física Ciências biológicas ii Ciências biológicas i Cellular and molecular neuroscience Biotecnología Biological psychiatry
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: gerard.muntane@urv.cat lourdes.martorell@urv.cat elisabet.vilella@urv.cat selena.aranda@estudiants.urv.cat ester.sada@estudiants.urv.cat ester.sada@estudiants.urv.cat
    Author identifier: 0000-0003-4999-2197 0000-0002-1887-5919
    Record's date: 2024-08-03
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.nature.com/articles/s41398-023-02508-0
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Translational Psychiatry. 13 (1): 201-201
    APA: Sada-Fuente, E; Aranda, S; Papiol, S; Heilbronner, U; Moltó, MD; Aguilar, EJ; González-Peñas, J; Andreu-Bernabeu, A; Arango, C; Crespo-Facorro, B; Gon (2023). Common genetic variants contribute to heritability of age at onset of schizophrenia. Translational Psychiatry, 13(1), 201-201. DOI: 10.1038/s41398-023-02508-0
    Article's DOI: 10.1038/s41398-023-02508-0
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2023
    Publication Type: Journal Publications
  • Keywords:

    Biological Psychiatry,Cellular and Molecular Neuroscience,Psychiatry,Psychiatry and Mental Health
    Genome-wide association
    sex-differences
    risk
    psychosis
    of-onset
    metaanalysis
    copy number variants
    Saúde coletiva
    Psychiatry and mental health
    Psychiatry
    Psicología
    Nutrição
    Medicina ii
    Medicina i
    Linguística e literatura
    Interdisciplinar
    Engenharias iv
    Enfermagem
    Educação física
    Ciências biológicas ii
    Ciências biológicas i
    Cellular and molecular neuroscience
    Biotecnología
    Biological psychiatry
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