Structural Brain Imaging Studies Offer Clues about the Effects of the Shared Genetic Etiology among Neuropsychiatric Disorders
Nevena V. Radonjić,
Jonathan L. Hess,
Jan K. Buitelaar,
Christopher R. K. Ching,
Sanjay M Sisodiya,
Dan J. Stein,
Odile A. van den Heuvel,
Theo G.M. van Erp,
Daan van Rooij,
Dick J Veltman,
Paul M Thompson,
Stephen V Faraone
Posted 17 Oct 2019
bioRxiv DOI: 10.1101/809582
Posted 17 Oct 2019
Background: Genomewide association studies have found significant genetic correlations among many neuropsychiatric disorders. In contrast, we know much less about the degree to which structural brain alterations are similar among disorders and, if so, the degree to which such similarities have a genetic etiology. Methods: From the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium, we acquired standardized mean differences (SMDs) in regional brain volume and cortical thickness between cases and controls. We had data on 41 brain regions for: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), epilepsy, major depressive disorder (MDD), obsessive compulsive disorder (OCD) and schizophrenia (SCZ). These data had been derived from 24,360 patients and 37,425 controls. Results: The SMDs were significantly correlated between SCZ and BD, OCD, MDD, and ASD. MDD was positively correlated with BD and OCD. BD was positively correlated with OCD and negatively correlated with ADHD. These pairwise correlations among disorders were correlated with the corresponding pairwise correlations among disorders derived from genomewide association studies (r = 0.49). Conclusions: Our results show substantial similarities in sMRI phenotypes among neuropsychiatric disorders and suggest that these similarities are accounted for, in part, by corresponding similarities in common genetic variant architectures. ### Competing Interest Statement Acknowledgment Dr. Faraone is supported by the European Union Horizon 2020 program for the CoCa project (grant agreement no 667302). And NIMH grants 5R01MH101519 and U01 MH109536-01. Research Council of Norway (#223273). Dr. Franke is supported by a personal Vici grant from the Netherlands Organization for Scientific Research (NWO, grant number 91813669) and by a grant from the European Union Horizon 2020 program for the CoCa project (grant agreement no 667302). ENIGMA work is supported by NIH grants U54 EB020403 (PI: Thompson), R01 MH116147 (PI: Thompson) and R01MH117601 (MPIs: Jahanshad & Schmaal). Dr Hoogman is supported by a personal Veni grant from the Netherlands Organization for Scientific Research (NWO, grant number 91619115). Dr. Mcdonald is supported by NIH grants R01 NS065838 and R21 NS107739. P.Rovira is a recipient of a pre-doctoral fellowship from the Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR), Generalitat de Catalunya, Spain (2016FI_B 00899). Dr. Schmaal is supported by a NHMRC Career Development Fellowship (1140764). Dr Sisodiya is supported by Epilepsy Society, UK, and the work was partly undertaken at UCLH/UCL, which received a proportion of funding from the UK Department of Health's NIHR Biomedical Research Centres funding scheme). Dr. Van Erp is supported by NIH grants U54 EB020403 (PI: Thompson), R01 MH116147 (PI: Thompson), R01MH117601 (MPIs: Jahanshad & Schmaal), and R01MH121246 (MPIs: Turner, Van Erp, & Calhoun). Financial Disclosures Dr. Andreassen has received speaker's honorarium from Lundbeck and is a consultant to HealthLytix. In the past year, Dr. Faraone received income, potential income, travel expenses continuing education support and/or research support from Tris, Otsuka, Arbor, Ironshore, Shire, Akili Interactive Labs, Enzymotec, Sunovion, Supernus and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child's Mental Health, Oxford University Press: Schizophrenia: The Facts and Elsevier: ADHD Non-Pharmacologic Interventions. He is Program Director of www.adhdinadults.com. Dr. Franke received educational speaking fees from Medice. All other authors declare no conflict of interest.
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