Articles producció científica> Medicina i Cirurgia

Recent natural selection conferred protection against schizophrenia by non-antagonistic pleiotropy

  • Identification data

    Identifier: imarina:9330092
    Authors:
    Gonzalez-Penas, Javierde Hoyos, LuciaDiaz-Caneja, Covadonga MAndreu-Bernabeu, AlvaroStella, CarolGurriaran, XaquinFananas, LourdesBobes, JulioGonzalez-Pinto, AnaCrespo-Facorro, BenedictoMartorell, LourdesVilella, ElisabetMuntane, GerardDolores Molto, MariaGonzalez-Piqueras, Jose CarlosParellada, MaraArango, CelsoCostas, Javier
    Abstract:
    Schizophrenia is a debilitating psychiatric disorder associated with a reduced fertility and decreased life expectancy, yet common predisposing variation substantially contributes to the onset of the disorder, which poses an evolutionary paradox. Previous research has suggested balanced selection, a mechanism by which schizophrenia risk alleles could also provide advantages under certain environments, as a reliable explanation. However, recent studies have shown strong evidence against a positive selection of predisposing loci. Furthermore, evolutionary pressures on schizophrenia risk alleles could have changed throughout human history as new environments emerged. Here in this study, we used 1000 Genomes Project data to explore the relationship between schizophrenia predisposing loci and recent natural selection (RNS) signatures after the human diaspora out of Africa around 100,000 years ago on a genome-wide scale. We found evidence for significant enrichment of RNS markers in derived alleles arisen during human evolution conferring protection to schizophrenia. Moreover, both partitioned heritability and gene set enrichment analyses of mapped genes from schizophrenia predisposing loci subject to RNS revealed a lower involvement in brain and neuronal related functions compared to those not subject to RNS. Taken together, our results suggest non-antagonistic pleiotropy as a likely mechanism behind RNS that could explain the persistence of schizophrenia common predisposing variation in human populations due to its association to other non-psychiatric phenotypes.© 2023. Springer Nature Limited.
  • Others:

    Author, as appears in the article.: Gonzalez-Penas, Javier; de Hoyos, Lucia; Diaz-Caneja, Covadonga M; Andreu-Bernabeu, Alvaro; Stella, Carol; Gurriaran, Xaquin; Fananas, Lourdes; Bobes, Julio; Gonzalez-Pinto, Ana; Crespo-Facorro, Benedicto; Martorell, Lourdes; Vilella, Elisabet; Muntane, Gerard; Dolores Molto, Maria; Gonzalez-Piqueras, Jose Carlos; Parellada, Mara; Arango, Celso; Costas, Javier
    Department: Medicina i Cirurgia
    URV's Author/s: Martorell Bonet, Lourdes / Vilella Cuadrada, Elisabet
    Keywords: Schizophrenia Humans Fertility Brain Bipolar disorder Alleles Africa partitioning heritability methylation genome scans evolution dna brain association annotation adaptation
    Abstract: Schizophrenia is a debilitating psychiatric disorder associated with a reduced fertility and decreased life expectancy, yet common predisposing variation substantially contributes to the onset of the disorder, which poses an evolutionary paradox. Previous research has suggested balanced selection, a mechanism by which schizophrenia risk alleles could also provide advantages under certain environments, as a reliable explanation. However, recent studies have shown strong evidence against a positive selection of predisposing loci. Furthermore, evolutionary pressures on schizophrenia risk alleles could have changed throughout human history as new environments emerged. Here in this study, we used 1000 Genomes Project data to explore the relationship between schizophrenia predisposing loci and recent natural selection (RNS) signatures after the human diaspora out of Africa around 100,000 years ago on a genome-wide scale. We found evidence for significant enrichment of RNS markers in derived alleles arisen during human evolution conferring protection to schizophrenia. Moreover, both partitioned heritability and gene set enrichment analyses of mapped genes from schizophrenia predisposing loci subject to RNS revealed a lower involvement in brain and neuronal related functions compared to those not subject to RNS. Taken together, our results suggest non-antagonistic pleiotropy as a likely mechanism behind RNS that could explain the persistence of schizophrenia common predisposing variation in human populations due to its association to other non-psychiatric phenotypes.© 2023. Springer Nature Limited.
    Thematic Areas: Zootecnia / recursos pesqueiros Saúde coletiva Química Psicología Odontología Nutrição Multidisciplinary sciences Multidisciplinary Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Matemática / probabilidade e estatística Letras / linguística Interdisciplinar Geografía Geociências Farmacia Engenharias iv Engenharias iii Engenharias ii Enfermagem Educação física Educação Economia Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Ciência da computação Biotecnología Biodiversidade Astronomia / física
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: lourdes.martorell@urv.cat elisabet.vilella@urv.cat
    Author identifier: 0000-0003-4999-2197 0000-0002-1887-5919
    Record's date: 2025-02-19
    Paper version: info:eu-repo/semantics/publishedVersion
    Paper original source: Scientific Reports. 13 (1): 15500-15500
    APA: Gonzalez-Penas, Javier; de Hoyos, Lucia; Diaz-Caneja, Covadonga M; Andreu-Bernabeu, Alvaro; Stella, Carol; Gurriaran, Xaquin; Fananas, Lourdes; Bobes, (2023). Recent natural selection conferred protection against schizophrenia by non-antagonistic pleiotropy. Scientific Reports, 13(1), 15500-15500. DOI: 10.1038/s41598-023-42578-0
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2023
    Publication Type: Journal Publications
  • Keywords:

    Multidisciplinary,Multidisciplinary Sciences
    Schizophrenia
    Humans
    Fertility
    Brain
    Bipolar disorder
    Alleles
    Africa
    partitioning heritability
    methylation
    genome scans
    evolution
    dna
    brain
    association
    annotation
    adaptation
    Zootecnia / recursos pesqueiros
    Saúde coletiva
    Química
    Psicología
    Odontología
    Nutrição
    Multidisciplinary sciences
    Multidisciplinary
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Materiais
    Matemática / probabilidade e estatística
    Letras / linguística
    Interdisciplinar
    Geografía
    Geociências
    Farmacia
    Engenharias iv
    Engenharias iii
    Engenharias ii
    Enfermagem
    Educação física
    Educação
    Economia
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Ciências agrárias i
    Ciência de alimentos
    Ciência da computação
    Biotecnología
    Biodiversidade
    Astronomia / física
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