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 at Chapel Hill

Ruth Huh

The University of North Carolina at Chapel Hill

Nikolay Oskolkov

Lund University

Jia Wen

The University of North Carolina at Chapel Hill

Sergiu Netotea

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Paola Giusti-Rodriguez

The University of North Carolina at Chapel Hill

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 at Chapel Hill

Martilias Farrell

The University of North Carolina at Chapel Hill

James J. Crowley

Karolinska Institutet

The University of North Carolina at Chapel Hill

Yun Li

The University of North Carolina at Chapel Hill

Patrik K.E. Magnusson

Karolinska Institutet

Ulf Gyllensten

Uppsala University

Christina M. Hultman

Karolinska Institutet

Patrick F. Sullivan

Karolinska Institutet

The University of North Carolina at Chapel Hill

Jin P. Szatkiewicz

The University of North Carolina at Chapel Hill

Nature Communications

2041-1723 (ISSN)

Vol. 11 1 1842-

Subject Categories

Medical Genetics

Bioinformatics and Systems Biology

Genetics

DOI

10.1038/s41467-020-15707-w

PubMed

32296054

More information

Latest update

5/26/2020