Cortical differences across psychiatric disorders and associated common and rare genetic variants
Year: 2025
Type: preprint
Study design: Observational Study
Abstract: Genetic studies have identified common and rare variants increasing the risk for neurodevelopmental and psychiatric disorders (NPDs). These risk variants have also been shown to influence the structure of the cerebral cortex. However, it is unknown whether cortical differences associated with genetic variants are linked to the risk they confer for NPDs. To answer this question, we analyzed cortical thickness (CT) and surface area (SA) for common and rare variants associated with NPDs, in ~33000 individuals from the general population and clinical cohorts, as well as ENIGMA summary statistics for 8 NPDs. Rare and common genetic variants increasing risk for NPDs were preferentially associated with total SA, while NPDs were preferentially associated with mean CT. Larger effects on mean CT, but not total SA, were observed in NPD medicated subgroups. At the regional level, genetic variants were preferentially associated with effects in sensorimotor areas, while NPDs showed higher effects in association areas. We show that schizophrenia- and bipolar-disorder-associated SNPs show positive and negative effect sizes on SA suggesting that their aggregated effects cancel out in additive polygenic models. Overall, CT and SA differences associated with NPDs do not relate to those observed across individual genetic variants and may be linked with critical non-genetic factors, such as medication and the lived experience of the disorder.
Source: medRxiv
Authors: Kuldeep Kumar, Zhijie Liao, Jakub Kopal, Clara Moreau, Christopher R. K. Ching, Claudia Modenato, Will Snyder, Sayeh Kazem, Charles-Olivier Martin, Anne-Marie Bélanger, Valérie K. Fontaine, Khadije Jizi, Rune Boen, Guillaume Huguet, Zohra Saci, Leila Kushan, Ana I. Silva, Marianne B.M. van den Bree, David E.J. Linden, Michael J. Owen, Jeremy Hall, Sarah Lippé, Guillaume Dumas, Bogdan Draganski, Laura Almasy, Sophia I. Thomopoulos, Neda Jahanshad, Ida E. Sønderby, Ole A. Andreassen, David C. Glahn, Armin Raznahan, Carrie E. Bearden, Tomas Paus, Paul M. Thompson, Sébastien Jacquemont
Institutions: Centre Hospitalier Universitaire Sainte-Justine, CHU Sainte-Justine Research Center, Université de Montréal, University of Oslo, University of Southern California, Centre Hospitalier Universitaire Vaudois, University of Lausanne, National Institutes of Health, University of Cambridge, National Institute of Mental Health, University of California, Los Angeles, University of Minnesota, Cardiff University, Maastricht University, University of Bern, University Hospital of Bern, Max Planck Institute for Human Cognitive and Brain Sciences, Children's Hospital of Philadelphia, University of Pennsylvania Health System, University of Pennsylvania, Oslo University Hospital, Boston Children's Hospital, Harvard University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Fondation Brain Canada, Wellcome Trust, Health and Care Research Wales, Compute Canada, Simons Foundation Autism Research Initiative, European Commission, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Norges Forskningsråd, Centre Hospitalier Universitaire Vaudois, Canada First Research Excellence Fund, Institut de Valorisation des Données, National Institutes of Health, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Helse Sør-Øst RHF, National Institute of Mental Health, National Institute of Biomedical Imaging and Bioengineering
Awards: How can local agroecological food systems contribute to food sovereignty in northwestern Argentina?, G1793114910, G1849255358, Integration of Five Large-Scale Neuropsychiatric Genetic Datasets under the RDoC Framework, Emergence of cognitive and brain structure alterations in carriers of an autism genetic risk factor at the 16p11.2 locus, ENIGMA-COINSTAC: Advanced Worldwide Transdiagnostic Analysis of Valence System Brain Circuit, G2811660202, G304045356, G3277956970, G3433676821, G3501664122, Reduced Certification Costs for Trusted Multi-core Platforms, G4537160225, G4762955193, G4869032613, DEFINE - Defining endophenotypes from integrated neurosciences, The two faces of neuroplasticity - In vivo study of brain plasticity induced by epileptic seizures and electroconvulsive therapy, Urban maps of the brain - the impact of city living on brain anatomy, mental and cognitive health -, ENIGMA Center for Worldwide Medicine, Imaging & Genomics, G67063899, Anatomical and functional segregation within cortico-basal ganglia circuits, G700495459, G7010676623, Making the “lazy” eye work: video game induced brain plasticity in amblyopia, Predicting comorbid cardiovascular disease in individuals with mental disorder by decoding disease mechanisms, G7048141691, Large-Scale Evaluation of the Effect of Rare Genetic Variants on Psychiatric Symptoms and Cognitive Ability, G732411733, Redefine Trans-Neuropsychiatric Disorder Brain Patterns through Big-Data and Machine Learning, G7473548085, G8008090399, Inter-Brain Synchronization: from Measurements to Mechanisms, G9000011481, G9000250461, Understanding Rare Genetic Variation and Disease Risk: A Global Neurogenetics Initiative, Neurodevelopment and Psychosis in the 22q11.2 Copy Number Variants
OpenAlex ID: W7108200775