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bioRxiv · 10.1101/2022.12.20.521181

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

Tissink, E.·Shadrin, A. A.·van der Meer, D.·Parker, N.·Hindley, G.·Roelfs, D.·Frei, O.·Fan, C. C.·Nagel, M.·Naerland, T.·Budisteanu, M.·Djurovic, S.·Westlye, L. T.·van den Heuvel, M.·Posthuma, D.·Kaufmann, T.·Dale, A. M.·Andreassen, O.
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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. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=192 SRC="FIGDIR/small/521181v3_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@1e7eadcorg.highwire.dtl.DTLVardef@ec127eorg.highwire.dtl.DTLVardef@b21f14org.highwire.dtl.DTLVardef@1690c5_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Tissink, E., Shadrin, A. A., van der Meer, D., Parker, N., Hindley, G., Roelfs, D., Frei, O., Fan, C. C., Nagel, M., Naerland, T., Budisteanu, M., Djurovic, S., Westlye, L. T., van den Heuvel, M., Posthuma, D., Kaufmann, T., Dale, A. M., Andreassen, O.. 2022-12-20. Abundant pleiotropy across neuroimaging modalities identified through a multivariate genome-wide association study. https://doi.org/10.1101/2022.12.20.521181

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