Increased burden of ultra-rare structural variants localizing to boundaries of topologically associated domains in schizophrenia

Research output: Contribution to journalArticle


Despite considerable progress in schizophrenia genetics, most findings have been for large rare structural variants and common variants in well-imputed regions with few genes implicated from exome sequencing. Whole genome sequencing (WGS) can potentially provide a more complete enumeration of etiological genetic variation apart from the exome and regions of high linkage disequilibrium. We analyze high-coverage WGS data from 1162 Swedish schizophrenia cases and 936 ancestry-matched population controls. Our main objective is to evaluate the contribution to schizophrenia etiology from a variety of genetic variants accessible to WGS but not by previous technologies. Our results suggest that ultra-rare structural variants that affect the boundaries of topologically associated domains (TADs) increase risk for schizophrenia. Alterations in TAD boundaries may lead to dysregulation of gene expression. Future mechanistic studies will be needed to determine the precise functional effects of these variants on biology.


  • Matthew Halvorsen
  • Ruth Huh
  • Nikolay Oskolkov
  • Jia Wen
  • Sergiu Netotea
  • Paola Giusti-Rodriguez
  • Robert Karlsson
  • Julien Bryois
  • Björn Nystedt
  • Adam Ameur
  • Anna K. Kähler
  • Na Eshia Ancalade
  • Martilias Farrell
  • James J. Crowley
  • Yun Li
  • Patrik K.E. Magnusson
  • Ulf Gyllensten
  • Christina M. Hultman
  • Patrick F. Sullivan
  • Jin P. Szatkiewicz
External organisations
  • University of North Carolina
  • Chalmers University of Technology
  • Karolinska Institutet
  • Uppsala University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Psychiatry
  • Medical Genetics
Original languageEnglish
Article number1842
JournalNature Communications
Issue number1
Publication statusPublished - 2020
Publication categoryResearch