2022
Exploring the clinical and genetic associations of adult weight trajectories using electronic health records in a racially diverse biobank: a phenome-wide and polygenic risk study
Xu J, Johnson JS, Signer R, Consortium E, Birgegård A, Jordan J, Kennedy MA, Landén M, Maguire SL, Martin NG, Mortensen PB, Petersen LV, Thornton LM, Bulik CM, Huckins LM. Exploring the clinical and genetic associations of adult weight trajectories using electronic health records in a racially diverse biobank: a phenome-wide and polygenic risk study. The Lancet Digital Health 2022, 4: e604-e614. PMID: 35780037, PMCID: PMC9612590, DOI: 10.1016/s2589-7500(22)00099-1.Peer-Reviewed Original ResearchConceptsElectronic health recordsPolygenic risk scoresWeight trajectoriesDepression polygenic risk scoresObesity polygenic risk scoresHealth recordsWeight changeUK BiobankIndividual health statusLower disease riskGenetic associationPatient populationUS National InstitutesWeight managementStable weightRisk scoreHealthy populationHealth statusAnorexia nervosaBioMe BiobankDisease riskDisorder diagnosisMental healthWeight lossPhenome-wide association studyWhat next for eating disorder genetics? Replacing myths with facts to sharpen our understanding
Huckins LM, Signer R, Johnson J, Wu YK, Mitchell KS, Bulik CM. What next for eating disorder genetics? Replacing myths with facts to sharpen our understanding. Molecular Psychiatry 2022, 27: 3929-3938. PMID: 35595976, PMCID: PMC9718676, DOI: 10.1038/s41380-022-01601-y.Peer-Reviewed Original ResearchAltered gene expression and PTSD symptom dimensions in World Trade Center responders
Marchese S, Cancelmo L, Diab O, Cahn L, Aaronson C, Daskalakis NP, Schaffer J, Horn SR, Johnson JS, Schechter C, Desarnaud F, Bierer LM, Makotkine I, Flory JD, Crane M, Moline JM, Udasin IG, Harrison DJ, Roussos P, Charney DS, Koenen KC, Southwick SM, Yehuda R, Pietrzak RH, Huckins LM, Feder A. Altered gene expression and PTSD symptom dimensions in World Trade Center responders. Molecular Psychiatry 2022, 27: 2225-2246. PMID: 35177824, DOI: 10.1038/s41380-022-01457-2.Peer-Reviewed Original ResearchConceptsPTSD symptom dimensionsPosttraumatic stress disorderCAPS scoresAnxious arousal symptomsSymptom dimensionsWorld Trade Center rescueClinician-Administered PTSD Scale scoresBiomarker of PTSDArousal symptomsCD4 T cellsWorld Trade Center respondersDevelopment of PTSDTotal CAPS scoresCase/control statusTherapeutic target developmentIdentification of biomarkersClinical interview dataResponder cohortPTSD symptom severityPotential biological differencesWTC respondersT cellsGene expressionPTSD studiesPsychiatric disorders
2021
Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk
Powell SK, O’Shea C, Townsley K, Prytkova I, Dobrindt K, Elahi R, Iskhakova M, Lambert T, Valada A, Liao W, Ho SM, Slesinger PA, Huckins LM, Akbarian S, Brennand KJ. Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk. Molecular Psychiatry 2021, 28: 1970-1982. PMID: 34493831, PMCID: PMC8898985, DOI: 10.1038/s41380-021-01273-0.Peer-Reviewed Original ResearchConceptsInduced dopaminergic neuronsDopaminergic neuronsMidbrain dopaminergic neuron developmentNeuron identityHuman induced pluripotent stem cellsCannabis use disorderDopaminergic neuron developmentAction potential durationGlutamatergic neuronsDopamine synthesisSpontaneous burstsPotential durationUse disordersNeuronal subtypesPsychiatric diseasesBipolar disorderElectrophysiological propertiesDisease riskHyperpolarization potentialPsychiatric disease riskNeuron developmentOscillatory activityNeuronsHeterogenous cell populationsCell populations
2020
Massively parallel techniques for cataloguing the regulome of the human brain
Townsley KG, Brennand KJ, Huckins LM. Massively parallel techniques for cataloguing the regulome of the human brain. Nature Neuroscience 2020, 23: 1509-1521. PMID: 33199899, PMCID: PMC8018778, DOI: 10.1038/s41593-020-00740-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRegulatory elementsTarget genesParallel reporter assaysPutative regulatory elementsNon-coding regionsDisease-associated lociSpecific expression patternsCandidate risk lociPluripotent stem cellsHigh-throughput assaysRelevant molecular pathwaysTranscriptional responseRegulatory architectureRisk lociExpression patternsReporter assaysComplex brain disordersMolecular pathwaysRegulomeStem cellsRisk architectureGenetic riskGenesLociGenetic diagnosis
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 effectsGene expression imputation across multiple brain regions provides insights into schizophrenia risk
Huckins LM, Dobbyn A, Ruderfer DM, Hoffman G, Wang W, Pardiñas AF, Rajagopal VM, Als TD, T. Nguyen H, Girdhar K, Boocock J, Roussos P, Fromer M, Kramer R, Domenici E, Gamazon ER, Purcell S, Demontis D, Børglum A, Walters J, O’Donovan M, Sullivan P, Owen M, Devlin B, Sieberts S, Cox N, Im H, Sklar P, Stahl E. Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. Nature Genetics 2019, 51: 659-674. PMID: 30911161, PMCID: PMC7034316, DOI: 10.1038/s41588-019-0364-4.Peer-Reviewed Original Research