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

González-Peñas, J., De Hoyos, L., Díaz-Caneja, C. M., Andreu-Bernabeu, Á., Stella, C., Gurriarán, X., et al. (2023). Recent natural selection conferred protection against schizophrenia by non-antagonistic pleiotropy. Scientific Reports, 13: 15500. doi:10.1038/s41598-023-42578-0.

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González-Peñas, Javier1, 2, 3, Autor
De Hoyos, Lucía4, 5, 6, Autor           
Díaz-Caneja, Covadonga M.1, 2, 3, 7, Autor
Andreu-Bernabeu, Álvaro1, 2, 7, Autor
Stella, Carol1, 2, Autor
Gurriarán, Xaquín1, 2, Autor
Fañanás, Lourdes3, 8, Autor
Bobes, Julio3, 9, Autor
González-Pinto, Ana3, 10, Autor
Crespo-Facorro, Benedicto3, 11, Autor
Martorell, Lourdes3, 12, Autor
Vilella, Elisabet3, 12, Autor
Muntané, Gerard3, 12, Autor
Molto, María Dolores3, 13, Autor
Gonzalez-Piqueras, Jose Carlos3, 13, 14, Autor
Parellada, Mara1, 2, 3, 7, Autor
Arango, Celso1, 2, 3, 7, Autor
Costas, Javier15, Autor
Affiliations:
1Hospital General Universitario Gregorio Marañón, Madrid, Spain, ou_persistent22              
2Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain, ou_persistent22              
3CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain , ou_persistent22              
4Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society, ou_792549              
5Population genetics of human communication, MPI for Psycholinguistics, Max Planck Society, ou_2579694              
6International Max Planck Research School for Language Sciences, MPI for Psycholinguistics, Max Planck Society, Nijmegen, NL, ou_1119545              
7Universidad Complutense, Madrid, Spain, ou_persistent22              
8University of Barcelona, Barcelona, Spain, ou_persistent22              
9Universidad de Oviedo, Oviedo, Spain, ou_persistent22              
10University of the Basque Country, Vitoria, Spain, ou_persistent22              
11Universidad de Sevilla, Sevilla, Spain, ou_persistent22              
12Universitat Rovira I Virgili, Reus, Spain, ou_persistent22              
13Universitat de València, Valencia, Spain, ou_persistent22              
14Fundación Investigación Hospital Clínico de Valencia, Valencia, Spain, ou_persistent22              
15Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Santiago de Compostela, Spain, ou_persistent22              

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 Zusammenfassung: 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.

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Sprache(n): eng - English
 Datum: 2023-09-19
 Publikationsstatus: Online veröffentlicht
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1038/s41598-023-42578-0
 Art des Abschluß: -

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Titel: Scientific Reports
  Kurztitel : Sci. Rep.
Genre der Quelle: Zeitschrift
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Affiliations:
Ort, Verlag, Ausgabe: London, UK : Nature Publishing Group
Seiten: - Band / Heft: 13 Artikelnummer: 15500 Start- / Endseite: - Identifikator: ISSN: 2045-2322
CoNE: https://pure.mpg.de/cone/journals/resource/2045-2322