The shared genetic architecture of schizophrenia, bipolar disorder and lifespan

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• dc.contributor.author Muntané, Gerard
• dc.contributor.author Farré, Xavier
• dc.contributor.author Bosch Fusté, Elena
• dc.contributor.author Martorell, Lourdes
• dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-
• dc.contributor.author Vilella, Elisabet
• dc.date.accessioned 2022-02-14T07:43:21Z
• dc.date.available 2022-02-14T07:43:21Z
• dc.date.issued 2021
• dc.description.abstract 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Muntané G, Farré X, Bosch E, Martorell L, Navarro A, Vilella E. The shared genetic architecture of schizophrenia, bipolar disorder and lifespan. Hum Genet. 2021;140(3):441-55. DOI: 10.1007/s00439-020-02213-8
• dc.identifier.doi http://dx.doi.org/10.1007/s00439-020-02213-8
• dc.identifier.issn 0340-6717
• dc.identifier.uri http://hdl.handle.net/10230/52482
• dc.language.iso eng
• dc.publisher Springer
• dc.relation.ispartof Hum Genet. 2021;140(3):441-55
• dc.rights © Springer The final publication is available at Springer via http://dx.doi.org/10.1007/s00439-020-02213-8.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.title The shared genetic architecture of schizophrenia, bipolar disorder and lifespan
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion