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Genetic Markers of Human Evolution Are Enriched in Schizophrenia

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Genetic Markers of Human Evolution Are Enriched in Schizophrenia. / Schizophrenia Working Group of the Psychiatric Genomics Consortium, The International Headache Genetics Consortium.
In: Biological Psychiatry, Vol. 80, No. 4, 15.08.2016, p. 284-92.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Schizophrenia Working Group of the Psychiatric Genomics Consortium, The International Headache Genetics Consortium 2016, 'Genetic Markers of Human Evolution Are Enriched in Schizophrenia', Biological Psychiatry, vol. 80, no. 4, pp. 284-92. https://doi.org/10.1016/j.biopsych.2015.10.009

APA

Schizophrenia Working Group of the Psychiatric Genomics Consortium, The International Headache Genetics Consortium (2016). Genetic Markers of Human Evolution Are Enriched in Schizophrenia. Biological Psychiatry, 80(4), 284-92. https://doi.org/10.1016/j.biopsych.2015.10.009

Vancouver

Schizophrenia Working Group of the Psychiatric Genomics Consortium, The International Headache Genetics Consortium. Genetic Markers of Human Evolution Are Enriched in Schizophrenia. Biological Psychiatry. 2016 Aug 15;80(4):284-92. Epub 2015 Oct 21. doi: 10.1016/j.biopsych.2015.10.009

Author

Schizophrenia Working Group of the Psychiatric Genomics Consortium, The International Headache Genetics Consortium. / Genetic Markers of Human Evolution Are Enriched in Schizophrenia. In: Biological Psychiatry. 2016 ; Vol. 80, No. 4. pp. 284-92.

Bibtex

@article{f0818ef7bfad45b28e368b799bc50447,
title = "Genetic Markers of Human Evolution Are Enriched in Schizophrenia",
abstract = "BACKGROUND: Why schizophrenia has accompanied humans throughout our history despite its negative effect on fitness remains an evolutionary enigma. It is proposed that schizophrenia is a by-product of the complex evolution of the human brain and a compromise for humans' language, creative thinking, and cognitive abilities.METHODS: We analyzed recent large genome-wide association studies of schizophrenia and a range of other human phenotypes (anthropometric measures, cardiovascular disease risk factors, immune-mediated diseases) using a statistical framework that draws on polygenic architecture and ancillary information on genetic variants. We used information from the evolutionary proxy measure called the Neanderthal selective sweep (NSS) score.RESULTS: Gene loci associated with schizophrenia are significantly (p = 7.30 × 10(-9)) more prevalent in genomic regions that are likely to have undergone recent positive selection in humans (i.e., with a low NSS score). Variants in brain-related genes with a low NSS score confer significantly higher susceptibility than variants in other brain-related genes. The enrichment is strongest for schizophrenia, but we cannot rule out enrichment for other phenotypes. The false discovery rate conditional on the evolutionary proxy points to 27 candidate schizophrenia susceptibility loci, 12 of which are associated with schizophrenia and other psychiatric disorders or linked to brain development.CONCLUSIONS: Our results suggest that there is a polygenic overlap between schizophrenia and NSS score, a marker of human evolution, which is in line with the hypothesis that the persistence of schizophrenia is related to the evolutionary process of becoming human.",
keywords = "Biological Evolution, Brain, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Schizophrenia, Journal Article",
author = "Saurabh Srinivasan and Francesco Bettella and Morten Mattingsdal and Yunpeng Wang and Aree Witoelar and Schork, {Andrew J} and Thompson, {Wesley K} and Verena Zuber and Winsvold, {Bendik S} and John-Anker Zwart and Collier, {David A} and Desikan, {Rahul S} and Ingrid Melle and Thomas Werge and Dale, {Anders M} and Srdjan Djurovic and Andreassen, {Ole A} and Jo Knight and {Schizophrenia Working Group of the Psychiatric Genomics Consortium, The International Headache Genetics Consortium}",
note = "Copyright {\textcopyright} 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.",
year = "2016",
month = aug,
day = "15",
doi = "10.1016/j.biopsych.2015.10.009",
language = "English",
volume = "80",
pages = "284--92",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "4",

}

RIS

TY - JOUR

T1 - Genetic Markers of Human Evolution Are Enriched in Schizophrenia

AU - Srinivasan, Saurabh

AU - Bettella, Francesco

AU - Mattingsdal, Morten

AU - Wang, Yunpeng

AU - Witoelar, Aree

AU - Schork, Andrew J

AU - Thompson, Wesley K

AU - Zuber, Verena

AU - Winsvold, Bendik S

AU - Zwart, John-Anker

AU - Collier, David A

AU - Desikan, Rahul S

AU - Melle, Ingrid

AU - Werge, Thomas

AU - Dale, Anders M

AU - Djurovic, Srdjan

AU - Andreassen, Ole A

AU - Knight, Jo

AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium, The International Headache Genetics Consortium

N1 - Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PY - 2016/8/15

Y1 - 2016/8/15

N2 - BACKGROUND: Why schizophrenia has accompanied humans throughout our history despite its negative effect on fitness remains an evolutionary enigma. It is proposed that schizophrenia is a by-product of the complex evolution of the human brain and a compromise for humans' language, creative thinking, and cognitive abilities.METHODS: We analyzed recent large genome-wide association studies of schizophrenia and a range of other human phenotypes (anthropometric measures, cardiovascular disease risk factors, immune-mediated diseases) using a statistical framework that draws on polygenic architecture and ancillary information on genetic variants. We used information from the evolutionary proxy measure called the Neanderthal selective sweep (NSS) score.RESULTS: Gene loci associated with schizophrenia are significantly (p = 7.30 × 10(-9)) more prevalent in genomic regions that are likely to have undergone recent positive selection in humans (i.e., with a low NSS score). Variants in brain-related genes with a low NSS score confer significantly higher susceptibility than variants in other brain-related genes. The enrichment is strongest for schizophrenia, but we cannot rule out enrichment for other phenotypes. The false discovery rate conditional on the evolutionary proxy points to 27 candidate schizophrenia susceptibility loci, 12 of which are associated with schizophrenia and other psychiatric disorders or linked to brain development.CONCLUSIONS: Our results suggest that there is a polygenic overlap between schizophrenia and NSS score, a marker of human evolution, which is in line with the hypothesis that the persistence of schizophrenia is related to the evolutionary process of becoming human.

AB - BACKGROUND: Why schizophrenia has accompanied humans throughout our history despite its negative effect on fitness remains an evolutionary enigma. It is proposed that schizophrenia is a by-product of the complex evolution of the human brain and a compromise for humans' language, creative thinking, and cognitive abilities.METHODS: We analyzed recent large genome-wide association studies of schizophrenia and a range of other human phenotypes (anthropometric measures, cardiovascular disease risk factors, immune-mediated diseases) using a statistical framework that draws on polygenic architecture and ancillary information on genetic variants. We used information from the evolutionary proxy measure called the Neanderthal selective sweep (NSS) score.RESULTS: Gene loci associated with schizophrenia are significantly (p = 7.30 × 10(-9)) more prevalent in genomic regions that are likely to have undergone recent positive selection in humans (i.e., with a low NSS score). Variants in brain-related genes with a low NSS score confer significantly higher susceptibility than variants in other brain-related genes. The enrichment is strongest for schizophrenia, but we cannot rule out enrichment for other phenotypes. The false discovery rate conditional on the evolutionary proxy points to 27 candidate schizophrenia susceptibility loci, 12 of which are associated with schizophrenia and other psychiatric disorders or linked to brain development.CONCLUSIONS: Our results suggest that there is a polygenic overlap between schizophrenia and NSS score, a marker of human evolution, which is in line with the hypothesis that the persistence of schizophrenia is related to the evolutionary process of becoming human.

KW - Biological Evolution

KW - Brain

KW - Genetic Markers

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Multifactorial Inheritance

KW - Polymorphism, Single Nucleotide

KW - Schizophrenia

KW - Journal Article

U2 - 10.1016/j.biopsych.2015.10.009

DO - 10.1016/j.biopsych.2015.10.009

M3 - Journal article

C2 - 26681495

VL - 80

SP - 284

EP - 292

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 4

ER -