Abundant pleiotropy across neuroimaging modalities identified through a multivariate genome-wide association study.

Journal: Nature communications

Volume: 15

Issue: 1

Year of Publication: 2024

Affiliated Institutions:  Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, HV, Amsterdam, The Netherlands. e.p.tissink@vu.nl. NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building , Oslo, Norway. Laureate Institute for Brain Research, Tulsa, OK, USA. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, HV, Amsterdam, The Netherlands. K.G. Jebsen Centre for Neurodevelopmental disorders, Division of Paediatric Medicine, Institute of Clinical Medicine, University of Oslo, Building , Oslo, Norway. Prof. Dr. Alex Obregia Clinical Hospital of Psychiatry, Bucharest, Romania. Department of Radiology, University of California San Diego, La Jolla, CA, , USA. NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building , Oslo, Norway. ole.andreassen@medisin.uio.no.

Abstract summary 

Genetic pleiotropy is abundant across spatially distributed brain characteristics derived from one neuroimaging modality (e.g. structural, functional or diffusion magnetic resonance imaging [MRI]). A better understanding of pleiotropy across modalities could inform us on the integration of brain function, micro- and macrostructure. Here we show extensive genetic overlap across neuroimaging modalities at a locus and gene level in the UK Biobank (N = 34,029) and ABCD Study (N = 8607). When jointly analysing phenotypes derived from structural, functional and diffusion MRI in a genome-wide association study (GWAS) with the Multivariate Omnibus Statistical Test (MOSTest), we boost the discovery of loci and genes beyond previously identified effects for each modality individually. Cross-modality genes are involved in fundamental biological processes and predominantly expressed during prenatal brain development. We additionally boost prediction of psychiatric disorders by conditioning independent GWAS on our multimodal multivariate GWAS. These findings shed light on the shared genetic mechanisms underlying variation in brain morphology, functional connectivity, and tissue composition.

Authors & Co-authors:  Tissink Shadrin van der Meer Parker Hindley Roelfs Frei Fan Nagel Nærland Budisteanu Djurovic Westlye van den Heuvel Posthuma Kaufmann Dale Andreassen

Study Outcome 

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Citations :  Tononi G, Edelman GM, Sporns O. Complexity and coherency: Integrating information in the brain. Trends Cogn. Sci. 1998;2:474–484. doi: 10.1016/S1364-6613(98)01259-5.
Authors :  18
Identifiers
Doi : 2655
SSN : 2041-1723
Study Population
Male,Female
Mesh Terms
Humans
Other Terms
Study Design
Study Approach
Country of Study
Publication Country
England