ArticleNeuroImage2021
Vertex-wise multivariate genome-wide association study identifies 780 unique genetic loci associated with cortical morphology.
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In one paragraph
Article in NeuroImage, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 6 of them syntheses that pooled it.
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80citing papers in PubMed, 6 pooled it
15.4field-weighted citation impact, top 1% of its field
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Who cites it
80 citing papers in PubMed, 6 syntheses or guidelines pooled it, 122 citations in OpenAlex.
- The multimodal neuroimaging signatures and gene expression profiles for adverse childhood experiences.BMC medicine · 2025Pooled it
- Multi-ancestry genome-wide association analyses incorporating SNP-by-psychosocial interactions identify novel loci for serum lipids.Translational psychiatry · 2025Pooled it
- A meta-analysis of genome-wide studies of resilience in the German population.Molecular psychiatry · 2025Pooled it
- Identification and validation of supervariants reveal novel loci associated with human white matter microstructure.Genome research · 2024Pooled it
- Genetic susceptibility to cognitive decline following craniospinal irradiation for pediatric central nervous system tumors.Neuro-oncology · 2023Pooled it
- Genome-wide association study meta-analysis of suicide death and suicidal behavior.Molecular psychiatry · 2023Pooled it
- Cross-ancestry pleiotropic analysis of imaging-derived phenotypes enhances risk stratification of depression.Molecular psychiatry · 2026Article
- Neural Cell Models of Specific Reading Disabilities: Identification of Cellular and Transcriptome Alterations.Genes, brain, and behavior · 2026Article
- Common alleles associated with connectivity within and across the brain's main functional networks.Nature communications · 2026Article
- Genetic architecture of white matter microstructure captured by unsupervised deep representation learning of fractional anisotropy maps.Nature communications · 2026Article
- A decade of discovery: Leveraging genomic data in the ABCD study to illuminate adolescent neurodevelopment.Developmental cognitive neuroscience · 2026Review
- HiFiMAP: High-resolution fast identity-by-descent mapping test.medRxiv : the preprint server for health sciences · 2026Article
- Learning dynamics of unsupervised deep learning reveal epoch-specific genetic architectures of brain morphology.bioRxiv : the preprint server for biology · 2026Article
- Genome-wide association study of delay discounting identifies 11 loci and reveals transdiagnostic associations across mental and physical health.Molecular psychiatry · 2026Article
- BRD1 haploinsufficiency alters early neuronal programming and disrupts maturation in human induced glutamatergic neurons.Research square · 2026Article
- Identifying genome-by-childhood trauma interactions for depression using a forest-based approach in the UK Biobank and Adolescent Brain Cognitive Development Study.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Integration of metabolomic and genetic data reveals novel variants underpinning the human metabolome: the Coronary Artery Risk Development in Young Adults (CARDIA) study.medRxiv : the preprint server for health sciences · 2026Article
- Insights into Dysregulated GABAergic Synapses and Depression: A Complex and Evolving Relationship.Advances in experimental medicine and biology · 2026Review
- Genetic and epigenetic analysis of plasma glial fibrillary acidic protein (GFAP) levels in PTSD.Molecular psychiatry · 2026Article
- Mapping rare protein-coding variants on multi-organ imaging traits.Nature communications · 2025Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 3 countries.
Alexey A ShadrinNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway. Electronic address: a.a.shadrin@medisin.uio.no.
Tobias KaufmannNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway.
Dennis van der MeerNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway; School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, the Netherlands.
Clare E PalmerDepartment of Neurosciences, University of California San Diego, La Jolla, CA 92037, USA; Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA 92037, USA.
Carolina MakowskiDepartment of Radiology, University of California San Diego, La Jolla, CA 92037, USA; Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA 92037, USA.
Robert LoughnanDepartment of Cognitive Science, University of California San Diego, La Jolla, CA 92037, USA.
Terry L JerniganCenter for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA 92037, USA; Center for Human Development, University of California San Diego, La Jolla, CA 92037, USA; Department of Cognitive Science, University of California San Diego, La Jolla, CA 92037, USA.
Tyler M SeibertDepartment of Radiology, University of California San Diego, La Jolla, CA 92037, USA; Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA 92037, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA 92037, USA; Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA 92037, USA.
Donald J HaglerDepartment of Radiology, University of California San Diego, La Jolla, CA 92037, USA; Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA 92037, USA.
Olav B SmelandNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway.
Ehsan MotazediNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway.
Yunhan ChuNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway.
Aihua LinNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway.
Weiqiu ChengNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway.
Guy HindleyNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway.
Wesley K ThompsonNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway; Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA 92037, USA.
Chun C FanCenter for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA 92037, USA.
Dominic HollandDepartment of Neurosciences, University of California San Diego, La Jolla, CA 92037, USA; Department of Radiology, University of California San Diego, La Jolla, CA 92037, USA; Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA 92037, USA.
Lars T WestlyeNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
Oleksandr FreiNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway.
Ole A AndreassenNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway. Electronic address: ole.andreassen@medisin.uio.no.
Anders M DaleNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway; Department of Neurosciences, University of California San Diego, La Jolla, CA 92037, USA; Department of Radiology, University of California San Diego, La Jolla, CA 92037, USA; Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA 92037, USA. Electronic address: andersmdale@gmail.com.
University of California, San Diego · USUniversity of Oslo · NOOslo University Hospital · NOMaastricht University · NL
Funding
ABCD-USA Consortium: Coordinating CenterU24DA041147 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SANDRA A BROWN, TERRY L. JERNIGAN · 2015 to 2026
$54.7MABCD-USA Consortium: Data Analysis, Informatics and Resource CenterU24DA041123 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ANDERS M DALE · 2015 to 2026
$51.5MAdolescent Substance Use Initiation: Disentangling neurocognitive risks from consequences using longitudinal and genetically-informed methodsU01DA041120 · NIDA · UNIVERSITY OF MINNESOTA · PI Monica Luciana, Sylia Wilson · 2015 to 2026
$34.5MABCD-USA Consortium: Research ProjectU01DA041089 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Joanna Jacobus, Susan F. Tapert · 2015 to 2026
$31.7MProspective Research Studies of Maturation (PRISM)- Research ProjectU01DA041134 · NIDA · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI ERIN MCGLADE, PERRY FRANKLIN RENSHAW · 2015 to 2026
$29.2MABCD-USA CONSORTIUM: RESEARCH PROJECTU01DA041048 · NIDA · CHILDREN'S HOSPITAL OF LOS ANGELES · PI Megan Marie Herting, ELIZABETH R SOWELL · 2015 to 2026
$28.7MABCD-USA Consortium: Research ProjectU01DA041106 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mary M Heitzeg, Chandra Sekhar Sripada · 2015 to 2026
$24.9MFIU-ABCD: Pathways and Mechanisms to Addiction in the Latino Youth of South FloridaU01DA041156 · NIDA · FLORIDA INTERNATIONAL UNIVERSITY · PI Raul Gonzalez, Angela R Laird · 2015 to 2026
$22.8MABCD-USA Consortium: Research ProjectU01DA041148 · NIDA · OREGON HEALTH & SCIENCE UNIVERSITY · PI Damien A Fair, Rebekah S Huber · 2015 to 2026
$22.3MABCD-USA: NYC Research ProjectU01DA041174 · NIDA · YALE UNIVERSITY · PI Arielle Ryan Baskin-Sommers, Betty J Casey · 2015 to 2026
$19.7MAdolescent Brain Cognitive Development (ABCD) Prospective Research in Studies of Maturation (PRISM) ConsortiumU01DA041117 · NIDA · UNIVERSITY OF MARYLAND BALTIMORE · PI LINDA CHANG, THOMAS M ERNST · 2015 to 2026
$19.5M15/21 ABCD-USA Consortium: Research Project Site at LIBRU01DA050989 · NIDA · LAUREATE INSTITUTE FOR BRAIN RESEARCH · PI ROBIN L AUPPERLE, MARTIN P. PAULUS · 2020 to 2026
$14.7MMedical Research Council MC_PC_17228Medical Research Council MC_QA137853NIDA NIH HHS U01 DA041022NIDA NIH HHS U01 DA041025NIDA NIH HHS U01 DA041028NIDA NIH HHS U01 DA041048NIDA NIH HHS U01 DA041089NIDA NIH HHS U01 DA041093NIDA NIH HHS U01 DA041106NIDA NIH HHS U01 DA041117NIDA NIH HHS U01 DA041120NIDA NIH HHS U01 DA041134NIDA NIH HHS U01 DA041148NIDA NIH HHS U01 DA041156NIDA NIH HHS U01 DA041174NIDA NIH HHS U01 DA050988NIDA NIH HHS U01 DA050989NIDA NIH HHS U01 DA051038NIDA NIH HHS U01 DA051039NIDA NIH HHS U24 DA041123NIDA NIH HHS U24 DA041147NIGMS NIH HHS R01 GM104400NIMH NIH HHS R01 MH100351
Abstract
Brain morphology has been shown to be highly heritable, yet only a small portion of the heritability is explained by the genetic variants discovered so far. Here we extended the Multivariate Omnibus Statistical Test (MOSTest) and applied it to genome-wide association studies (GWAS) of vertex-wise structural magnetic resonance imaging (MRI) cortical measures from N=35,657 participants in the UK Biobank. We identified 695 loci for cortical surface area and 539 for cortical thickness, in total 780 unique genetic loci associated with cortical morphology robustly replicated in 8,060 children of mixed ethnicity from the Adolescent Brain Cognitive Development (ABCD) Study®. This reflects more than 8-fold increase in genetic discovery at no cost to generalizability compared to the commonly used univariate GWAS methods applied to region of interest (ROI) data. Functional follow up including gene-based analyses implicated 10% of all protein-coding genes and pointed towards pathways involved in neurogenesis and cell differentiation. Power analysis indicated that applying the MOSTest to vertex-wise structural MRI data triples the effective sample size compared to conventional univariate GWAS approaches. The large boost in power obtained with the vertex-wise MOSTest together with pronounced replication rates and highlighted biologically meaningful pathways underscores the advantage of multivariate approaches in the context of highly distributed polygenic architecture of the human brain.
Indexed as
AgedCerebral CortexChildFemaleGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMagnetic Resonance ImagingMaleMiddle AgedMultifactorial InheritanceNeuroimagingUnited KingdomCortical surface areaCortical thicknessDistributed polygenic architectureGenome-wide association studyMultivariate vertex-wise analysis
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