Increased burden of ultra-rare structural variants localizing to boundaries of topologically associated domains in schizophrenia
Journal article, 2020
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.
Author
Matthew Halvorsen
The University of North Carolina System
Ruth Huh
The University of North Carolina System
Nikolay Oskolkov
Lund University
Jia Wen
The University of North Carolina System
Sergiu Netotea
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Paola Giusti-Rodriguez
The University of North Carolina System
Robert Karlsson
Karolinska Institutet
Julien Bryois
Karolinska Institutet
Björn Nystedt
Uppsala University
Adam Ameur
Uppsala University
Anna K. Kähler
Karolinska Institutet
Na Eshia Ancalade
The University of North Carolina System
Martilias Farrell
The University of North Carolina System
James J. Crowley
The University of North Carolina System
Karolinska Institutet
Yun Li
The University of North Carolina System
Patrik K.E. Magnusson
Karolinska Institutet
Ulf Gyllensten
Uppsala University
Christina M. Hultman
Karolinska Institutet
Patrick F. Sullivan
The University of North Carolina System
Karolinska Institutet
Jin P. Szatkiewicz
The University of North Carolina System
Nature Communications
2041-1723 (ISSN) 20411723 (eISSN)
Vol. 11 1 1842- 1842Subject Categories (SSIF 2011)
Medical Genetics
Bioinformatics and Systems Biology
Genetics
DOI
10.1038/s41467-020-15707-w
PubMed
32296054