Genetic Markers of Human Evolution Are Enriched in Schizophrenia
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Genetic Markers of Human Evolution Are Enriched in Schizophrenia. / Srinivasan, Saurabh; Bettella, Francesco; Mattingsdal, Morten; Wang, Yunpeng; Witoelar, Aree; Schork, Andrew J; Thompson, Wesley K; Zuber, Verena; Winsvold, Bendik S; Zwart, John-Anker; Collier, David A; Desikan, Rahul S; Melle, Ingrid; Werge, Thomas; Dale, Anders M; Djurovic, Srdjan; Andreassen, Ole A.; Schizophrenia Working Group of the Psychiatric Genomics Consortium, The International Headache Genetics Consortium.
I: Biological Psychiatry, Bind 80, Nr. 4, 15.08.2016, s. 284-92.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 - 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 - 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 -
ID: 178989838