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The role of rare copy number variants in depression

By Kendall Kimberley M, Elliott Rees, Matthew Bracher-Smith, Lucy Riglin, Stanley Zammit, Michael C O’Donovan, Michael J. Owen, Ian Jones, George Kirov, James T. R. Walters

Posted 27 Jul 2018
bioRxiv DOI: 10.1101/378307

The role of large, rare copy number variants (CNVs) in neurodevelopmental disorders is well established, but their contribution to common psychiatric disorders, such as depression, remains unclear. We have previously shown that a substantial proportion of CNV enrichment in schizophrenia is explained by CNVs associated with neurodevelopmental disorders. Depression shares genetic risk with schizophrenia and is frequently comorbid with neurodevelopmental disorders, suggesting to us the hypothesis that if CNVs play a role in depression, neurodevelopmental CNVs are those most likely to be associated. We confirmed this in UK Biobank by showing that neurodevelopmental CNVs were associated with depression (24,575 cases, 5.87%; OR=1.36, 95% CI 1.22-1.51, p=1.61x10-8), whilst finding no evidence implicating other CNVs. Four individual neurodevelopmental CNVs increased risk of depression (1q21.1 duplication, PWS duplication, 16p13.11 deletion, 16p11.2 duplication). The association between neurodevelopmental CNVs and depression was partially explained by social deprivation but not by education attainment or physical illness.

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