Abstract
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.
| Original language | English |
|---|---|
| Article number | 2655 |
| Pages (from-to) | 1-13 |
| Number of pages | 13 |
| Journal | Nature Communications |
| Volume | 15 |
| Early online date | 26 Mar 2024 |
| DOIs | |
| Publication status | Published - 2024 |
Bibliographical note
Publisher Copyright:© The Author(s) 2024.
Funding
E.P.T. has been supported by the Foundation “De Drie Lichten” and The Simons Foundation Fund in The Netherlands. This work was partly performed on the TSD (Tjeneste for Sensitive Data) facilities, owned by the University of Oslo, operated and developed by the TSD service group at the University of Oslo, IT Department (USIT) ([email protected]). We gratefully acknowledge support from the The Netherlands Organization for Scientific Research (NWO Gravitation: BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology - Grant No. 024.004.012, and VICI 452-16-015), The European Research Council (Advanced Grant No ERC-2018-AdG GWAS2FUNC 834057, Consolidator Grant No 101001062), American National Institutes of Health (NS057198, EB000790, 1R01MH124839, R01MH120025, R01MH122688), The Research Council of Norway (RCN) (229129, 213837, 324252, 300309, 273291, 223273, 248980, 276082, 323961), The South-East Norway Regional Health Authority (2019-108, 2022-073), KG Jebsen Stiftelsen (SKGJ-MED-021), EEA (#EEA2018-0573) collaborative grant in ASD: “Improving quality of life for Autism Spectrum Disorders patients by promoting strategies for early diagnosis and preventive measures” and EEA-RO-NO-Grant 2014–2021 (contract No 6/2019), and the European Union’s Horizon 2020 research and innovation programme (No 847776 and 964874 and 801133, Marie Sklodowska-Curie grant agreement). We want to acknowledge the participants and investigators of the UK Biobank, ABCD Study, TOP, BUPGEN, PGC and FinnGen studies. The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. We are grateful to all the participating families in Norway who take part in this on-going cohort study. We thank the Norwegian Institute of Public Health (NIPH) for generating high-quality genomic data. This research is part of the HARVEST collaboration, supported by the Research Council of Norway (#229624). Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development SM Study (ABCD Study®) (https://abcdstudy.org), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children aged 9-10 and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners under award numbers: U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147. A full list of supporters is available at https://abcdstudy.org/federal-partners/. A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/principal-investigators.html. ABCD Study consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD Study consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this came from [NIMH Data Archive Digital Object Identifier (10.15154/1519007)].
| Funders | Funder number |
|---|---|
| National Institute of Mental Health | |
| Simons Foundation Fund | |
| Helse- og Omsorgsdepartementet | |
| Universitetet i Oslo | |
| Norwegian Institute of Public Health | |
| Norges forskningsråd | 223273, 229129, 248980, 213837, 324252, 276082, 300309, 273291, 323961 |
| Nederlandse Organisatie voor Wetenschappelijk Onderzoek | 024.004.012, VICI 452-16-015 |
| European Research Council | ERC-2018-AdG GWAS2FUNC 834057, 101001062 |
| National Institutes of Health | U01DA041117, U01DA041106, U01DA041028, U24DA041147, U01DA041148, U01DA041048, U24DA041123, U01DA041156, U01DA041134, U01DA041089, U01DA041022, U01DA041120, U01DA041174 |
| European Environment Agency | #EEA2018-0573, 6/2019 |
| American National Institutes of Health | R01MH122688, 1R01MH124839, EB000790, NS057198, R01MH120025 |
| KG Jebsen Stiftelsen | SKGJ-MED-021 |
| Haridus- ja Teadusministeerium | 229624 |
| Horizon 2020 Framework Programme | 801133, 964874, 847776 |
| Helse Sør-Øst RHF | 2022-073, 2019-108 |