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 studiesGenes
2019
Synergistic effects of common schizophrenia risk variants
Schrode N, Ho SM, Yamamuro K, Dobbyn A, Huckins L, Matos MR, Cheng E, Deans PJM, Flaherty E, Barretto N, Topol A, Alganem K, Abadali S, Gregory J, Hoelzli E, Phatnani H, Singh V, Girish D, Aronow B, Mccullumsmith R, Hoffman GE, Stahl EA, Morishita H, Sklar P, Brennand KJ. Synergistic effects of common schizophrenia risk variants. Nature Genetics 2019, 51: 1475-1485. PMID: 31548722, PMCID: PMC6778520, DOI: 10.1038/s41588-019-0497-5.Peer-Reviewed Original ResearchMeSH KeywordsChloride ChannelsCRISPR-Cas SystemsFemaleFurinGene EditingGene Expression RegulationGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInduced Pluripotent Stem CellsMaleMonomeric Clathrin Assembly ProteinsPolymorphism, Single NucleotideQuantitative Trait LociSchizophreniaSNARE ProteinsConceptsExpression quantitative trait lociComplex genetic disorderEQTL genesCommon variantsQuantitative trait lociRisk variantsGene expression differencesPsychiatric disease riskCommon risk variantsPluripotent stem cellsSchizophrenia risk variantsGenetic disordersTrait lociGene perturbationsGenetic approachesExpression differencesGene editingStem cellsGeneralizable phenomenonSynaptic functionGenesVariantsCRISPRLociSpecific effects
2018
Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection
Pardiñas A, Holmans P, Pocklington A, Escott-Price V, Ripke S, Carrera N, Legge S, Bishop S, Cameron D, Hamshere M, Han J, Hubbard L, Lynham A, Mantripragada K, Rees E, MacCabe J, McCarroll S, Baune B, Breen G, Byrne E, Dannlowski U, Eley T, Hayward C, Martin N, McIntosh A, Plomin R, Porteous D, Wray N, Caballero A, Geschwind D, Huckins L, Ruderfer D, Santiago E, Sklar P, Stahl E, Won H, Agerbo E, Als T, Andreassen O, Bækvad-Hansen M, Mortensen P, Pedersen C, Børglum A, Bybjerg-Grauholm J, Djurovic S, Durmishi N, Pedersen M, Golimbet V, Grove J, Hougaard D, Mattheisen M, Molden E, Mors O, Nordentoft M, Pejovic-Milovancevic M, Sigurdsson E, Silagadze T, Hansen C, Stefansson K, Stefansson H, Steinberg S, Tosato S, Werge T, GERAD1 Consortium, CRESTAR Consortium, Collier D, Rujescu D, Kirov G, Owen M, O’Donovan M, Walters J. Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nature Genetics 2018, 50: 381-389. PMID: 29483656, PMCID: PMC5918692, DOI: 10.1038/s41588-018-0059-2.Peer-Reviewed Original ResearchConceptsMutation-intolerant genesGenetic architecture of schizophreniaGenome-wide association studiesChromosome conformation dataGenome fine mappingVariant association signalsAssociation signalsFine-mappingGenetic architectureCausal genesGenomic studiesAssociation studiesRisk variantsSelection pressureGenesLociBrain expressionAssociated with poor qualityBiologyConformational dataDecreased life expectancyChromosomeDebilitating psychiatric conditionAllelesLife expectancy