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Interrogating the Evolutionary Paradox of Schizophrenia: A Novel Framework and Evidence Supporting Recent Negative Selection of Schizophrenia Risk Alleles

Schizophrenia is a psychiatric disorder with a worldwide prevalence of ∼1%. The high heritability and reduced fertility among schizophrenia patients have raised an evolutionary paradox: why has negative selection not eliminated schizophrenia associated alleles during evolution? To address this quest...

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Autores principales: Liu, Chenxing, Everall, Ian, Pantelis, Christos, Bousman, Chad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502987/
https://www.ncbi.nlm.nih.gov/pubmed/31114607
http://dx.doi.org/10.3389/fgene.2019.00389
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author Liu, Chenxing
Everall, Ian
Pantelis, Christos
Bousman, Chad
author_facet Liu, Chenxing
Everall, Ian
Pantelis, Christos
Bousman, Chad
author_sort Liu, Chenxing
collection PubMed
description Schizophrenia is a psychiatric disorder with a worldwide prevalence of ∼1%. The high heritability and reduced fertility among schizophrenia patients have raised an evolutionary paradox: why has negative selection not eliminated schizophrenia associated alleles during evolution? To address this question, we examined evolutionary markers, known as modern-human-specific (MD) sites and archaic-human-specific sites, using existing genome-wide association study (GWAS) data from 34,241 individuals with schizophrenia and 45,604 healthy controls included in the Psychiatric Genomics Consortium (PGC). By testing the distribution of schizophrenia single nucleotide polymorphisms (SNPs) with risk and protective effects in the human-specific sites, we observed a negative selection of risk alleles for schizophrenia in modern humans relative to archaic humans (e.g., Neanderthal and Denisovans). Such findings indicate that risk alleles of schizophrenia have been gradually removed from the modern human genome due to negative selection pressure. This novel evidence contributes to our understanding of the genetic origins of schizophrenia.
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spelling pubmed-65029872019-05-21 Interrogating the Evolutionary Paradox of Schizophrenia: A Novel Framework and Evidence Supporting Recent Negative Selection of Schizophrenia Risk Alleles Liu, Chenxing Everall, Ian Pantelis, Christos Bousman, Chad Front Genet Genetics Schizophrenia is a psychiatric disorder with a worldwide prevalence of ∼1%. The high heritability and reduced fertility among schizophrenia patients have raised an evolutionary paradox: why has negative selection not eliminated schizophrenia associated alleles during evolution? To address this question, we examined evolutionary markers, known as modern-human-specific (MD) sites and archaic-human-specific sites, using existing genome-wide association study (GWAS) data from 34,241 individuals with schizophrenia and 45,604 healthy controls included in the Psychiatric Genomics Consortium (PGC). By testing the distribution of schizophrenia single nucleotide polymorphisms (SNPs) with risk and protective effects in the human-specific sites, we observed a negative selection of risk alleles for schizophrenia in modern humans relative to archaic humans (e.g., Neanderthal and Denisovans). Such findings indicate that risk alleles of schizophrenia have been gradually removed from the modern human genome due to negative selection pressure. This novel evidence contributes to our understanding of the genetic origins of schizophrenia. Frontiers Media S.A. 2019-04-30 /pmc/articles/PMC6502987/ /pubmed/31114607 http://dx.doi.org/10.3389/fgene.2019.00389 Text en Copyright © 2019 Liu, Everall, Pantelis and Bousman. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Liu, Chenxing
Everall, Ian
Pantelis, Christos
Bousman, Chad
Interrogating the Evolutionary Paradox of Schizophrenia: A Novel Framework and Evidence Supporting Recent Negative Selection of Schizophrenia Risk Alleles
title Interrogating the Evolutionary Paradox of Schizophrenia: A Novel Framework and Evidence Supporting Recent Negative Selection of Schizophrenia Risk Alleles
title_full Interrogating the Evolutionary Paradox of Schizophrenia: A Novel Framework and Evidence Supporting Recent Negative Selection of Schizophrenia Risk Alleles
title_fullStr Interrogating the Evolutionary Paradox of Schizophrenia: A Novel Framework and Evidence Supporting Recent Negative Selection of Schizophrenia Risk Alleles
title_full_unstemmed Interrogating the Evolutionary Paradox of Schizophrenia: A Novel Framework and Evidence Supporting Recent Negative Selection of Schizophrenia Risk Alleles
title_short Interrogating the Evolutionary Paradox of Schizophrenia: A Novel Framework and Evidence Supporting Recent Negative Selection of Schizophrenia Risk Alleles
title_sort interrogating the evolutionary paradox of schizophrenia: a novel framework and evidence supporting recent negative selection of schizophrenia risk alleles
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502987/
https://www.ncbi.nlm.nih.gov/pubmed/31114607
http://dx.doi.org/10.3389/fgene.2019.00389
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