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Title

Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion

Authors
Cleynen, Isabelle
Engchuan, Worrawat
Hestand, Matthew S
Heung, Tracy
Holleman, Aaron M
Johnston, H Richard
Monfeuga, Thomas
McDonald-McGinn, Donna M
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Collaboration
Published in Molecular Psychiatry. 2020
Abstract Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10-6). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.
Identifiers
PMID: 32015465
Full text
Article (Published version) (3.2 MB) - document accessible for UNIGE members only Limited access to UNIGE
Other version: https://www.nature.com/articles/s41380-020-0654-3
Structures
Research groups Laboratoire d'imagerie et de psychopathologie développementale (693)
NCCR Synapsy
Projects
FNS: 324730_144260
FNS: 51NF40-185897
Citation
(ISO format)
CLEYNEN, Isabelle et al. Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion. In: Molecular Psychiatry, 2020. doi: 10.1038/s41380-020-0654-3 https://archive-ouverte.unige.ch/unige:138349

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Deposited on : 2020-07-10

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