2024
W22. EATING DISORDERS OVER THE WEIGHT SPECTRUM: DISSECTING GENETIC DIFFERENCES OF EATING DISORDERS, THINNESS, AND OBESITY
Xu J, Signer R, Hicks E, Johnston K, Termorshuizen J, Group P, Bulik C, Huckins L. W22. EATING DISORDERS OVER THE WEIGHT SPECTRUM: DISSECTING GENETIC DIFFERENCES OF EATING DISORDERS, THINNESS, AND OBESITY. European Neuropsychopharmacology 2024, 87: 112. DOI: 10.1016/j.euroneuro.2024.08.231.Peer-Reviewed Original ResearchTissue-specific mannerSignificant genesCC-GWASGenetic distanceConstitutional thinnessIdentified multiple risk variantsBonferroni significanceGenome-wide lociGenome-wide significanceMultiple risk variantsConcordant effect directionsBinge eatingClinical differencesEating disordersGTEx v8S-PrediXcanAN-BGene associationsGenetic relationshipsRisk variantsRisk genesWeight-related traitsGenetic etiologyGenesDifferential expression
2023
56. USING HIPSC-NEURONS AND CRISPR TO UNCOVER NON-ADDITIVE EFFECTS OF SCZ RISK GENES
Deans M, Seah C, Johnson J, García-González J, Townsley K, Cao E, Schrode N, Stahl E, O'Reilly P, Huckins L, Brennand K. 56. USING HIPSC-NEURONS AND CRISPR TO UNCOVER NON-ADDITIVE EFFECTS OF SCZ RISK GENES. European Neuropsychopharmacology 2023, 75: s86. DOI: 10.1016/j.euroneuro.2023.08.162.Peer-Reviewed Original ResearchSCZ risk genesNon-additive effectsRisk genesCombinatorial perturbationsTranscriptomic effectsFunctional roleRisk variantsGene expression changesBulk RNA-seqMultiple functional rolesSynaptic functionHigh-throughput imagingFunctional redundancyTranscriptional regulatorsRNA-seqCRISPR activationCellular phenotypesRNA interferenceEGenesGene expressionExpression changesHiPSC neuronsPolygenic risk scoresGenetic studiesGenesSchizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations
Liu D, Meyer D, Fennessy B, Feng C, Cheng E, Johnson J, Park Y, Rieder M, Ascolillo S, de Pins A, Dobbyn A, Lebovitch D, Moya E, Nguyen T, Wilkins L, Hassan A, Burdick K, Buxbaum J, Domenici E, Frangou S, Hartmann A, Laurent-Levinson C, Malhotra D, Pato C, Pato M, Ressler K, Roussos P, Rujescu D, Arango C, Bertolino A, Blasi G, Bocchio-Chiavetto L, Campion D, Carr V, Fullerton J, Gennarelli M, González-Peñas J, Levinson D, Mowry B, Nimgaokar V, Pergola G, Rampino A, Cervilla J, Rivera M, Schwab S, Wildenauer D, Daly M, Neale B, Singh T, O’Donovan M, Owen M, Walters J, Ayub M, Malhotra A, Lencz T, Sullivan P, Sklar P, Stahl E, Huckins L, Charney A. Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations. Nature Genetics 2023, 55: 369-376. PMID: 36914870, PMCID: PMC10011128, DOI: 10.1038/s41588-023-01305-1.Peer-Reviewed Original ResearchConceptsProtein-truncating variantsRare protein-truncating variantsControls of diverse ancestryGenetic architecture of schizophreniaRare variant signalsProtein-coding regionsSchizophrenia risk genesCustom sequencing panelAncestral populationsAllelic spectrumGenetic architectureHuman populationDiverse ancestryHuman geneticsRisk genesVariant signalsGenesSequencing panelSchizophrenia casesSchizophrenia riskChronic mental illnessAncestryGeneticsMental illnessVariants
2017
Integrated Bayesian analysis of rare exonic variants to identify risk genes for schizophrenia and neurodevelopmental disorders
Nguyen H, Bryois J, Kim A, Dobbyn A, Huckins L, Munoz-Manchado A, Ruderfer D, Genovese G, Fromer M, Xu X, Pinto D, Linnarsson S, Verhage M, Smit A, Hjerling-Leffler J, Buxbaum J, Hultman C, Sklar P, Purcell S, Lage K, He X, Sullivan P, Stahl E. Integrated Bayesian analysis of rare exonic variants to identify risk genes for schizophrenia and neurodevelopmental disorders. Genome Medicine 2017, 9: 114. PMID: 29262854, PMCID: PMC5738153, DOI: 10.1186/s13073-017-0497-y.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsDD risk genesRisk genesRisk-geneGene set enrichment resultsProtein-protein interaction subnetworksStudy of rare variationWhole-exome sequencing dataNeurodevelopmental disorder genesPost-transcriptional gene regulationExome sequencing dataSets of genesRare exonic variantsGene set enrichmentRare variationNeurodevelopmental disordersAutism spectrum disorderGene subnetworksGenetic architectureSequence dataRNA-seqTrio familiesGene regulationExonic variantsPathway enrichmentNovel Bipolar And Schizophrenia Risk Genes Identified Through Genic Associations In Transcriptome Imputation
Huckins L, Dobbyn A, Ruderfer D, Fromer M, Consortium C, Cox N, Im H, Sieberts S, Devlin B, Roussos P, Purcell S, Sklar P, Stahl E. Novel Bipolar And Schizophrenia Risk Genes Identified Through Genic Associations In Transcriptome Imputation. European Neuropsychopharmacology 2017, 27: s487. DOI: 10.1016/j.euroneuro.2016.09.577.Peer-Reviewed Original ResearchPsychiatric Genomics ConsortiumGenome-wide significanceGenic associationsGene expressionAssociation studiesPsychiatric Genomics Consortium schizophreniaRisk genesLarge-scale transcriptome datasetsVariants regulate gene expressionBackgroundGenome-wide association studiesTissue-specific gene expression levelsGWAS sample sizeNovel risk genesRNA-seq dataBipolar disorderSchizophrenia risk genesBiologically relevant dataCase-control sampleGWAS lociGene expression levelsGenome-wideGWAS datasetDisease architectureGenomic regionsTop loci