Rare CNVs and phenome-wide profiling highlight brain structural divergence and phenotypical convergence

Jakub Kopal, Kuldeep Kumar, Karin Saltoun, Claudia Modenato, Clara A. Moreau, Sandra Martin-Brevet, Guillaume Huguet, Martineau Jean-Louis, Charles Olivier Martin, Zohra Saci, Nadine Younis, Petra Tamer, Elise Douard, Anne M. Maillard, Borja Rodriguez-Herreros, Aurèlie Pain, Sonia Richetin, Leila Kushan, Ana I. Silva, Marianne B.M. van den BreeDavid E.J. Linden, Michael J. Owen, Jeremy Hall, Sarah Lippé, Bogdan Draganski, Ida E. Sønderby, Ole A. Andreassen, David C. Glahn, Paul M. Thompson, Carrie E. Bearden, Sébastien Jacquemont, Danilo Bzdok

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Copy number variations (CNVs) are rare genomic deletions and duplications that can affect brain and behaviour. Previous reports of CNV pleiotropy imply that they converge on shared mechanisms at some level of pathway cascades, from genes to large-scale neural circuits to the phenome. However, existing studies have primarily examined single CNV loci in small clinical cohorts. It remains unknown, for example, how distinct CNVs escalate vulnerability for the same developmental and psychiatric disorders. Here we quantitatively dissect the associations between brain organization and behavioural differentiation across 8 key CNVs. In 534 CNV carriers, we explored CNV-specific brain morphology patterns. CNVs were characteristic of disparate morphological changes involving multiple large-scale networks. We extensively annotated these CNV-associated patterns with ~1,000 lifestyle indicators through the UK Biobank resource. The resulting phenotypic profiles largely overlap and have body-wide implications, including the cardiovascular, endocrine, skeletal and nervous systems. Our population-level investigation established brain structural divergences and phenotypical convergences of CNVs, with direct relevance to major brain disorders.

Original languageEnglish
Pages (from-to)1001-1017
Number of pages17
JournalNature Human Behaviour
Issue number6
StatePublished - Jun 2023
Externally publishedYes


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