The psychiatric phenotypes of 1q21 distal deletion and duplication: (see correction)

Stefanie C. Linden, Cameron J. Watson, Jacqueline Smith, Samuel J.R.A. Chawner, Thomas M. Lancaster, Ffion Evans, Nigel Williams, David Skuse, F. Lucy Raymond, Jeremy Hall, Michael J. Owen, David E.J. Linden, Lee Anne Green-Snyder, Wendy K. Chung, Anne M. Maillard, Sébastien Jacquemont, Marianne B.M. van den Bree

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Copy number variants are amongst the most highly penetrant risk factors for psychopathology and neurodevelopmental deficits, but little information about the detailed clinical phenotype associated with particular variants is available. We present the largest study of the microdeletion and -duplication at the distal 1q21 locus, which has been associated with schizophrenia and intellectual disability, in order to investigate the range of psychiatric phenotypes. Clinical and cognitive data from 68 deletion and 55 duplication carriers were analysed with logistic regression analysis to compare frequencies of mental disorders between carrier groups and controls, and linear mixed models to compare quantitative phenotypes. Both children and adults with copy number variants at 1q21 had high frequencies of psychopathology. In the children, neurodevelopmental disorders were most prominent (56% for deletion, 68% for duplication carriers). Adults had increased prevalence of mood (35% for deletion [OR = 6.6 (95% CI: 1.4–40.1)], 55% for duplication carriers [8.3 (1.4–55.5)]) and anxiety disorders (24% [1.8 (0.4–8.4)] and 55% [10.0 (1.9–71.2)]). The adult group, which included mainly genetically affected parents of probands, had an IQ in the normal range. These results confirm high prevalence of neurodevelopmental disorders associated with CNVs at 1q21 but also reveal high prevalence of mood and anxiety disorders in a high-functioning adult group with these CNVs. Because carriers of neurodevelopmental CNVs who show relevant psychopathology but no major cognitive impairment are not currently routinely receiving clinical genetic services widening of genetic testing in psychiatry may be considered.

Original languageEnglish
Article number105
JournalTranslational Psychiatry
Issue number1
Early online date14 Jan 2021
Publication statusPublished - 4 Feb 2021

Bibliographical note

Funding Information:
We thank all the children and parents who took part in the Intellectual Disability and Mental Health: Assessing the Genomic Impact on Neurodevelopment (IMAGINE-ID) study, as well as the members of the IMAGINE-ID consortium for their contributions. We are grateful for the UK National Health Service (NHS) medical genetic clinics for their support. We thank the core laboratory team of the Division of Psychological Medicine and Clinical Neurosciences Laboratory at Cardiff University (Cardiff, UK) for DNA sample management and genotyping. The Cardiff group is grateful for recruitment support to the charity ‘Unique’, a support group for people with rare chromosomal disorders. The New York group is grateful to all the families who participated in the Simons Variation in Individuals Project (Simons VIP), as well as the Simons VIP investigators. Approved researchers can obtain the Simons VIP datasets described in this study by applying at SPONSORSHIP: Cardiff cohort: Wellcome Trust Strategic Award “Defining endophenotypes from integrative neuroscience” (DEFINE, 100202/Z/12/Z), Medical Research Council (Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment (IMAGINE) study MR/N022572/1 and MR/L011166/1), by the Baily Thomas Charitable Trust (2315/1), the Waterloo Foundation (918-1234), Wellcome Trust ISSF grant, Medical Research Council Centre grant (G0801418) and Medical Research Council Programme grant (G0800509). Recruitment was supported by the National Centre for Mental Health, which is funded by Health and Care Research Wales (HCRW). Lausanne cohort/Jacquemont group: Swiss National Science Foundation (SNSF, grant PMPDP3_171331). Canada Research Chairs Programme. Brain Canada Multi-Investigator Research Initiative. New York/Simons VIP cohort: Support provided by the Simons Foundation Autism Research Initiative (SFARI).

Publisher Copyright:
© 2021, The Author(s).

Copyright 2021 Elsevier B.V., All rights reserved.

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry


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