The psychiatric phenotypes of 1q21 distal deletion and duplication
Lancaster, Thomas M.
Raymond, F. Lucy
Linden, David E. J.
Chung, Wendy K.
Nature Publishing Group UK
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Linden, S. C., Watson, C. J., Smith, J., Chawner, S. J. R. A., Lancaster, T. M., Evans, F., Williams, N., et al. (2021). The psychiatric phenotypes of 1q21 distal deletion and duplication. Translational Psychiatry, 11 (1)https://doi.org/10.1038/s41398-021-01226-9
Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265
Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440
Funder: Waterloo Foundation (TWF); doi: https://doi.org/10.13039/100012107
Funder: Health and Care Research Wales (Ymchwil Iechyd a Gofal Cymru); doi: https://doi.org/10.13039/100012068
Funder: Simons Foundation; doi: https://doi.org/10.13039/100000893
Abstract: 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.
Article, /692/420/2489, /692/699/476, /45, /45/61, article
External DOI: https://doi.org/10.1038/s41398-021-01226-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/324887