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