ArticleNeuroImage2022
Generalization of cortical MOSTest genome-wide associations within and across samples.
Article in NeuroImage, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Partitioning Fraction of Variance Explained into Strong Localized Effects and Weak Diffuse Effects.bioRxiv : the preprint server for biology · 2026Article
- A decade of discovery: Leveraging genomic data in the ABCD study to illuminate adolescent neurodevelopment.Developmental cognitive neuroscience · 2026Review
- The genetic architecture of human cerebellar morphology supports a key role for the cerebellum in human evolution and psychopathology.Communications biology · 2026Article
- Hemochromatosis neural archetype reveals iron disruption in motor circuits.Science advances · 2024Article
- Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.Nature genetics · 2024Article
- The genetic landscape of basal ganglia and implications for common brain disorders.Nature communications · 2024Article
- Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.medRxiv : the preprint server for health sciences · 2024Article
- Distributed genetic effects of the corpus callosum subregions suggest links to neuropsychiatric disorders and related traits.Acta neuropsychiatrica · 2023Article
- Genotype Data and Derived Genetic Instruments of Adolescent Brain Cognitive Development StudyBehavior genetics · 2023Article
- Mapping the genetic architecture of cortical morphology through neuroimaging: progress and perspectives.Translational psychiatry · 2022Review
- Distributed genetic architecture across the hippocampal formation implies common neuropathology across brain disorders.Nature communications · 2022Article
- The genetic architecture of human cortical folding.Science advances · 2021Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Genome-Wide Association studies have typically been limited to univariate analysis in which a single outcome measure is tested against millions of variants. Recent work demonstrates that a Multivariate Omnibus Statistic Test (MOSTest) is well powered to discover genomic effects distributed across multiple phenotypes. Applied to cortical brain MRI morphology measures, MOSTest has resulted in a drastic improvement in power to discover loci when compared to established approaches (min-P). One question that arises is how well these discovered loci replicate in independent data. Here we perform 10 times cross validation within 34,973 individuals from UK Biobank for imaging measures of cortical area, thickness and sulcal depth (>1,000 dimensionality for each). By deploying a replication method that aggregates discovered effects distributed across multiple phenotypes, termed PolyVertex Score (MOSTest-PVS), we demonstrate a higher replication yield and comparable replication rate of discovered loci for MOSTest (# replicated loci: 242-496, replication rate: 96-97%) in independent data when compared with the established min-P approach (# replicated loci: 26-55, replication rate: 91-93%). An out-of-sample replication of discovered loci was conducted with a sample of 4,069 individuals from the Adolescent Brain Cognitive Development® (ABCD) study, who are on average 50 years younger than UK Biobank individuals. We observe a higher replication yield and comparable replication rate of MOSTest-PVS compared to min-P. This finding underscores the importance of using well-powered multivariate techniques for both discovery and replication of high dimensional phenotypes in Genome-Wide Association studies.
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