Abstract
Genetic pleiotropy is abundant across spatially distributed brain characteristics derived from one neuroimaging modality (e.g. structural, functional or diffusion 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=8,607). When jointly analysing phenotypes derived from structural, functional and diffusion MRI 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.
Competing Interest Statement
E.P.T., A.A.S., D.v.d.M, N.P., G.H., D.R., O.F., C.C.F., M.N., T.N., M.B., S.D., L.T.W., M.P.v.d.H., D.P. and T.K. declare no conflicts of interest. Dr. Andreassen has received speaker's honorarium from Lundbeck and Janssen, and is a consultant to coretechs.ai. Dr. Dale is a Founder of and holds equity in CorTechs Labs, Inc, and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc. and receives funding through research agreements with General Electric Healthcare and Medtronic, Inc. The terms of these arrangements have been reviewed and approved by UCSD in accordance with its conflict of interest policies.
Footnotes
Revision of methods to assess polygenic score improvement. Revision of main text on condFDR.