title: Probing the Association between Early Evolutionary Markers and Schizophrenia.
abstract: Schizophrenia is suggested to be a by-product of the evolution in humans, a compromise for our language, creative thinking and cognitive abilities, and thus, essentially, a human disorder. The time of its origin during the course of human evolution remains unclear. Here we investigate several markers of early human evolution and their relationship to the genetic risk of schizophrenia. We tested the schizophrenia evolutionary hypothesis by analyzing genome-wide association studies of schizophrenia and other human phenotypes in a statistical framework suited for polygenic architectures. We analyzed evolutionary proxy measures: human accelerated regions, segmental duplications, and ohnologs, representing various time periods of human evolution for overlap with the human genomic loci associated with schizophrenia. Polygenic enrichment plots suggest a higher prevalence of schizophrenia associations in human accelerated regions, segmental duplications and ohnologs. However, the enrichment is mostly accounted for by linkage disequilibrium, especially with functional elements like introns and untranslated regions. Our results did not provide clear evidence that markers of early human evolution are more likely associated with schizophrenia. While SNPs associated with schizophrenia are enriched in HAR, Ohno and SD regions, the enrichment seems to be mediated by affiliation to known genomic enrichment categories. Taken together with previous results, these findings suggest that schizophrenia risk may have mainly developed more recently in human evolution.
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Srinivasan
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bettella
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Sahar
authors.initials: S
authors.lastname: Hassani
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Aree
authors.initials: A
authors.lastname: Witoelar
authors.affiliation: Multimodal Imaging Laboratory, University of California at San Diego, La Jolla, CA, United States of America.|Cognitive Sciences Graduate Program, University of California, San Diego, La Jolla, CA, United States of America.|Center for Human Development, University of California at San Diego, La Jolla, CA, United States of America.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Schork
authors.affiliation: Institute of Biological Psychiatry, Mental Health Center St. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.|The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Wesley K
authors.initials: WK
authors.lastname: Thompson
authors.affiliation: Eli Lilly & Co, Erl Wood Manor, Windlesham, Surrey, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Collier
authors.affiliation: Neuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States of America.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Desikan
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Melle
authors.affiliation: Multimodal Imaging Laboratory, University of California at San Diego, La Jolla, CA, United States of America.|Center for Human Development, University of California at San Diego, La Jolla, CA, United States of America.|Department of Neuroscience, University of California at San Diego, La Jolla, CA, United States of America.|Neuroradiology Section, Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, CA, United States of America.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.|NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.|Institute of Biological Psychiatry, Mental Health Center St. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
mesh_terms: D019143:Evolution, Molecular; D005260:Female; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D005819:Genetic Markers