Rxivist logo

Analysis of differentially methylated regions in primates and non-primates provides support for the evolutionary hypothesis of schizophrenia

By Niladri Banerjee, Tatiana Polushina, Francesco Bettella, Vidar M. Steen, Ole A Andreassen, Stephanie Le Hellard

Posted 15 May 2018
bioRxiv DOI: 10.1101/322693

Introduction: The persistence of schizophrenia in human populations separated by geography and time led to the evolutionary hypothesis that proposes schizophrenia as a by-product of the higher cognitive abilities of modern humans. To explore this hypothesis, we used here an evolutionary epigenetics approach building on differentially methylated regions (DMRs) of the genome. Methods: We implemented a polygenic enrichment testing pipeline using the summary statistics of genome-wide association studies (GWAS) of schizophrenia and 12 other phenotypes. We investigated the enrichment of association of these traits across genomic regions with variable methylation between modern humans and great apes (orangutans, chimpanzees and gorillas; primate DMRs) and between modern humans and recently extinct hominids (Neanderthals and Denisovans; non-primate DMRs). Results: Regions that are hypo-methylated in humans compared to great apes show enrichment of association with schizophrenia only if the major histocompatibility complex (MHC) region is included. With the MHC region removed from the analysis, only a modest enrichment for SNPs of low effect persists. The INRICH pipeline confirms this finding after rigorous permutation and bootstrapping procedures. Conclusion: The analyses of regions with differential methylation changes in humans and great apes do not provide compelling evidence of enrichment of association with schizophrenia, in contrast to our previous findings on more recent methylation differences between modern humans, Neanderthals and Denisovans. Our results further support the evolutionary hypothesis of schizophrenia and indicate that the origin of some of the genetic susceptibility factors of schizophrenia may lie in recent human evolution.

Download data

  • Downloaded 362 times
  • Download rankings, all-time:
    • Site-wide: 51,533 out of 100,745
    • In genomics: 4,328 out of 6,246
  • Year to date:
    • Site-wide: 80,544 out of 100,745
  • Since beginning of last month:
    • Site-wide: 66,294 out of 100,745

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


  • 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
  • 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
  • 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
  • 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
  • 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
  • 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
  • 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
  • 22 Jan 2019: Nature just published an article about Rxivist and our data.
  • 13 Jan 2019: The Rxivist preprint is live!