Articles producció científica> Medicina i Cirurgia

The shared genetic architecture of schizophrenia, bipolar disorder and lifespan

  • Dades identificatives

    Identificador: imarina:7474046
    Autors:
    Muntané GFarré XBosch EMartorell LNavarro AVilella E
    Resum:
    © 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Psychiatric disorders such as Schizophrenia (SCZ) and Bipolar Disorder (BD) represent an evolutionary paradox, as they exhibit strong negative effects on fitness, such as decreased fecundity and early mortality, yet they persist at a worldwide prevalence of approximately 1%. Molecular mechanisms affecting lifespan, which may be widely common among complex diseases with fitness effects, can be studied by the integrated analysis of data from genome-wide association studies (GWAS) of human longevity together with any disease of interest. Here, we report the first of such studies, focusing on the genetic overlap—pleiotropy—between two psychiatric disorders with shortened lifespan, SCZ and BD, and human parental lifespan (PLS) as a surrogate of life expectancy. Our results are twofold: first, we demonstrate extensive polygenic overlap between SCZ and PLS and to a lesser extent between BD and PLS. Second, we identified novel loci shared between PLS and SCZ (n = 39), and BD (n = 8). Whereas most of the identified SCZ (66%) and BD (62%) pleiotropic risk alleles were associated with reduced lifespan, we also detected some antagonistic protective alleles associated to shorter lifespans. In fact, top-associated SNPs with SCZ seems to explain longevity variance explained (LVE) better than many other life-threatening diseases, including Type 2 diabetes and most cancers, probably due to a high overlap with smoking-related pathways. Overall, our study provides evidence of a genetic burden driven through premature mortality among people with SCZ, which can have profound implications for understanding, and potentially treating, the mortality gap associated with this psychiatric disorder.
  • Altres:

    Autor segons l'article: Muntané G; Farré X; Bosch E; Martorell L; Navarro A; Vilella E
    Departament: Medicina i Cirurgia
    Autor/s de la URV: Martorell Bonet, Lourdes / Vilella Cuadrada, Elisabet
    Paraules clau: Worldwide Positive selection Mortality Metaanalysis Identification Heritability Genome-wide association Expectancy Common variants Adaptive evolution
    Resum: © 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Psychiatric disorders such as Schizophrenia (SCZ) and Bipolar Disorder (BD) represent an evolutionary paradox, as they exhibit strong negative effects on fitness, such as decreased fecundity and early mortality, yet they persist at a worldwide prevalence of approximately 1%. Molecular mechanisms affecting lifespan, which may be widely common among complex diseases with fitness effects, can be studied by the integrated analysis of data from genome-wide association studies (GWAS) of human longevity together with any disease of interest. Here, we report the first of such studies, focusing on the genetic overlap—pleiotropy—between two psychiatric disorders with shortened lifespan, SCZ and BD, and human parental lifespan (PLS) as a surrogate of life expectancy. Our results are twofold: first, we demonstrate extensive polygenic overlap between SCZ and PLS and to a lesser extent between BD and PLS. Second, we identified novel loci shared between PLS and SCZ (n = 39), and BD (n = 8). Whereas most of the identified SCZ (66%) and BD (62%) pleiotropic risk alleles were associated with reduced lifespan, we also detected some antagonistic protective alleles associated to shorter lifespans. In fact, top-associated SNPs with SCZ seems to explain longevity variance explained (LVE) better than many other life-threatening diseases, including Type 2 diabetes and most cancers, probably due to a high overlap with smoking-related pathways. Overall, our study provides evidence of a genetic burden driven through premature mortality among people with SCZ, which can have profound implications for understanding, and potentially treating, the mortality gap associated with this psychiatric disorder.
    Àrees temàtiques: Saúde coletiva Odontología Medicina ii Medicina i Interdisciplinar Genetics (clinical) Genetics & heredity Genetics General medicine Farmacia Engenharias iii Enfermagem Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología Biodiversidade
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 03406717
    Adreça de correu electrònic de l'autor: lourdes.martorell@urv.cat elisabet.vilella@urv.cat
    Identificador de l'autor: 0000-0003-4999-2197 0000-0002-1887-5919
    Data d'alta del registre: 2024-07-27
    Versió de l'article dipositat: info:eu-repo/semantics/acceptedVersion
    Enllaç font original: https://link.springer.com/article/10.1007%2Fs00439-020-02213-8
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Human Genetics. 140 (3): 441-455
    Referència de l'ítem segons les normes APA: Muntané G; Farré X; Bosch E; Martorell L; Navarro A; Vilella E (2021). The shared genetic architecture of schizophrenia, bipolar disorder and lifespan. Human Genetics, 140(3), 441-455. DOI: 10.1007/s00439-020-02213-8
    DOI de l'article: 10.1007/s00439-020-02213-8
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2021
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Genetics,Genetics & Heredity,Genetics (Clinical)
    Worldwide
    Positive selection
    Mortality
    Metaanalysis
    Identification
    Heritability
    Genome-wide association
    Expectancy
    Common variants
    Adaptive evolution
    Saúde coletiva
    Odontología
    Medicina ii
    Medicina i
    Interdisciplinar
    Genetics (clinical)
    Genetics & heredity
    Genetics
    General medicine
    Farmacia
    Engenharias iii
    Enfermagem
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Biotecnología
    Biodiversidade
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