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

Research output: Contribution to journalArticle


  • International 22q11.2DS Brain and Behavior Consortium

External Institution(s)

  • KU Leuven
  • University of Toronto
  • University of Cincinnati
  • Cincinnati Children's Hospital Medical Center
  • University Health Network
  • Emory University
  • Cardiff University
  • University of Pennsylvania
  • Yeshiva University
  • Utrecht University
  • University of California at Los Angeles
  • Deep Genomics
  • Maastricht University
  • Universidad de Chile
  • Universidad del Desarrollo
  • Royal College of Surgeons in Ireland
  • King's College London
  • University of Rome La Sapienza
  • IRCCS Ospedale pediatrico Bambino Gesù - Roma
  • Tel Aviv University
  • Sheba Medical Center at Tel Hashomer
  • Geha Mental Health Center
  • University of Pittsburgh
  • University of Geneva
  • Syracuse University
  • SUNY Upstate Medical University
  • Assistance publique - Hôpitaux de Marseille
  • Aix-Marseille Université
  • University of Newcastle
  • University of California at Davis
  • University of North Carolina at Chapel Hill
  • Duke University
  • Complutense University
  • Universidad Autónoma de Madrid
  • Hospital Son Dureta


Original languageEnglish (US)
JournalMolecular psychiatry
StatusAccepted/In press - Jan 1 2020


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.

Citation formats


International 22q11.2DS Brain and Behavior Consortium (Accepted/In press). Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion. Molecular psychiatry.


International 22q11.2DS Brain and Behavior Consortium 2020, 'Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion', Molecular psychiatry.