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Kopal, Jakub; Kumar, Kuldeep; Saltoun, Karin; Modenato, Claudia; Moreau, Clara A; Martin-Brevet, Sandra; Huguet, Guillaume; Jean-Louis, Martineau; Martin, Charles-Olivier; Saci, Zohra; Younis, Nadine; Tamer, Petra; Douard, Elise; Maillard, Anne M; Rodriguez-Herreros, Borja; Pain, Aurèlie; Richetin, Sonia; Kushan, Leila; Silva, Ana I; van den Bree, Marianne B M; Linden, David E J; Owen, Michael J; Hall, Jeremy; Lippé, Sarah; Draganski, Bogdan; Sønderby, Ida E; Andreassen, Ole A; Glahn, David C; Thompson, Paul M; Bearden, Carrie E; Jacquemont, Sébastien; Bzdok, Danilo
Nature human behaviour, 06/2023, Volume: 7, Issue: 6Journal Article
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.
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