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 ResearchPredicted gene expression in ancestrally diverse populations leads to discovery of susceptibility loci for lifestyle and cardiometabolic traits.
Highland HM, Wojcik GL, Graff M, Nishimura KK, Hodonsky CJ, Baldassari AR, Cote AC, Cheng I, Gignoux CR, Tao R, Li Y, Boerwinkle E, Fornage M, Haessler J, Hindorff LA, Hu Y, Justice AE, Lin BM, Lin D, Stram DO, Haiman CA, Kooperberg C, Le Marchand L, Matise TC, Kenny EE, Carlson CS, Stahl EA, Avery CL, North KE, Ambite JL, Buyske S, Loos RJ, Peters U, Young KL, Bien SA, Huckins LM. Predicted gene expression in ancestrally diverse populations leads to discovery of susceptibility loci for lifestyle and cardiometabolic traits. American Journal Of Human Genetics 2022, 109: 669-679. PMID: 35263625, PMCID: PMC9069067, DOI: 10.1016/j.ajhg.2022.02.013.Peer-Reviewed Original ResearchMapping anorexia nervosa genes to clinical phenotypes.
Johnson JS, Cote AC, Dobbyn A, Sloofman LG, Xu J, Cotter L, Charney AW, Birgegård A, Jordan J, Kennedy M, Landén M, Maguire SL, Martin NG, Mortensen PB, Thornton LM, Bulik CM, Huckins LM. Mapping anorexia nervosa genes to clinical phenotypes. Psychological Medicine 2022, 1-15. PMID: 35379376, DOI: 10.1017/S0033291721004554.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 disordersComparison of confound adjustment methods in the construction of gene co-expression networks
Cote AC, Young HE, Huckins LM. Comparison of confound adjustment methods in the construction of gene co-expression networks. Genome Biology 2022, 23: 44. PMID: 35115012, PMCID: PMC8812044, DOI: 10.1186/s13059-022-02606-0.Peer-Reviewed Original Research
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 diagnosisImplicit bias of encoded variables: frameworks for addressing structured bias in EHR-GWAS data.
Dueñas HR, Seah C, Johnson JS, Huckins LM. Implicit bias of encoded variables: frameworks for addressing structured bias in EHR-GWAS data. Human Molecular Genetics 2020, 29: R33-R41. PMID: 32879975, PMCID: PMC7530523, DOI: 10.1093/hmg/ddaa192.Peer-Reviewed Original ResearchAnalysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts.
Huckins LM, Chatzinakos C, Breen MS, Hartmann J, Klengel T, da Silva Almeida AC, Dobbyn A, Girdhar K, Hoffman GE, Klengel C, Logue MW, Lori A, Maihofer AX, Morrison FG, Nguyen HT, Park Y, Ruderfer D, Sloofman LG, van Rooij SJH, Baker DG, Chen CY, Cox N, Duncan LE, Geyer MA, Glatt SJ, Im HK, Risbrough VB, Smoller JW, Stein DJ, Yehuda R, Liberzon I, Koenen KC, Jovanovic T, Kellis M, Miller MW, Bacanu SA, Nievergelt CM, Buxbaum JD, Sklar P, Ressler KJ, Stahl EA, Daskalakis NP. Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts. Cell Reports 2020, 31: 107716. PMID: 32492425, PMCID: PMC7359754, DOI: 10.1016/j.celrep.2020.107716.Peer-Reviewed Original Research
2019
International Society of Psychiatric Genetics Ethics Committee: Issues facing us.
Lázaro-Muñoz G, Sabatello M, Huckins L, Peay H, Degenhardt F, Meiser B, Lencz T, Soda T, Docherty A, Crepaz-Keay D, Austin J, Peterson RE, Davis LK. International Society of Psychiatric Genetics Ethics Committee: Issues facing us. American Journal Of Medical Genetics. Part B, Neuropsychiatric Genetics : The Official Publication Of The International Society Of Psychiatric Genetics 2019, 180: 543-554. PMID: 31124312, PMCID: PMC6861601, DOI: 10.1002/ajmg.b.32736.Peer-Reviewed Original ResearchPenetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia in 106,160 Patients Across Four Health Care Systems.
Zheutlin AB, Dennis J, Karlsson Linnér R, Moscati A, Restrepo N, Straub P, Ruderfer D, Castro VM, Chen CY, Ge T, Huckins LM, Charney A, Kirchner HL, Stahl EA, Chabris CF, Davis LK, Smoller JW. Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia in 106,160 Patients Across Four Health Care Systems. The American Journal Of Psychiatry 2019, 176: 846-855. PMID: 31416338, PMCID: PMC6961974, DOI: 10.1176/appi.ajp.2019.18091085.Peer-Reviewed Original ResearchSynergistic 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 effectsGenome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa.
Watson HJ, Yilmaz Z, Thornton LM, Hübel C, Coleman JRI, Gaspar HA, Bryois J, Hinney A, Leppä VM, Mattheisen M, Medland SE, Ripke S, Yao S, Giusti-Rodríguez P, Hanscombe KB, Purves KL, Adan RAH, Alfredsson L, Ando T, Andreassen OA, Baker JH, Berrettini WH, Boehm I, Boni C, Perica VB, Buehren K, Burghardt R, Cassina M, Cichon S, Clementi M, Cone RD, Courtet P, Crow S, Crowley JJ, Danner UN, Davis OSP, de Zwaan M, Dedoussis G, Degortes D, DeSocio JE, Dick DM, Dikeos D, Dina C, Dmitrzak-Weglarz M, Docampo E, Duncan LE, Egberts K, Ehrlich S, Escaramís G, Esko T, Estivill X, Farmer A, Favaro A, Fernández-Aranda F, Fichter MM, Fischer K, Föcker M, Foretova L, Forstner AJ, Forzan M, Franklin CS, Gallinger S, Giegling I, Giuranna J, Gonidakis F, Gorwood P, Mayora MG, Guillaume S, Guo Y, Hakonarson H, Hatzikotoulas K, Hauser J, Hebebrand J, Helder SG, Herms S, Herpertz-Dahlmann B, Herzog W, Huckins LM, Hudson JI, Imgart H, Inoko H, Janout V, Jiménez-Murcia S, Julià A, Kalsi G, Kaminská D, Kaprio J, Karhunen L, Karwautz A, Kas MJH, Kennedy JL, Keski-Rahkonen A, Kiezebrink K, Kim YR, Klareskog L, Klump KL, Knudsen GPS, La Via MC, Le Hellard S, Levitan RD, Li D, Lilenfeld L, Lin BD, Lissowska J, Luykx J, Magistretti PJ, Maj M, Mannik K, Marsal S, Marshall CR, Mattingsdal M, McDevitt S, McGuffin P, Metspalu A, Meulenbelt I, Micali N, Mitchell K, Monteleone AM, Monteleone P, Munn-Chernoff MA, Nacmias B, Navratilova M, Ntalla I, O'Toole JK, Ophoff RA, Padyukov L, Palotie A, Pantel J, Papezova H, Pinto D, Rabionet R, Raevuori A, Ramoz N, Reichborn-Kjennerud T, Ricca V, Ripatti S, Ritschel F, Roberts M, Rotondo A, Rujescu D, Rybakowski F, Santonastaso P, Scherag A, Scherer SW, Schmidt U, Schork NJ, Schosser A, Seitz J, Slachtova L, Slagboom PE, Slof-Op 't Landt MCT, Slopien A, Sorbi S, Świątkowska B, Szatkiewicz JP, Tachmazidou I, Tenconi E, Tortorella A, Tozzi F, Treasure J, Tsitsika A, Tyszkiewicz-Nwafor M, Tziouvas K, van Elburg AA, van Furth EF, Wagner G, Walton E, Widen E, Zeggini E, Zerwas S, Zipfel S, Bergen AW, Boden JM, Brandt H, Crawford S, Halmi KA, Horwood LJ, Johnson C, Kaplan AS, Kaye WH, Mitchell JE, Olsen CM, Pearson JF, Pedersen NL, Strober M, Werge T, Whiteman DC, Woodside DB, Stuber GD, Gordon S, Grove J, Henders AK, Juréus A, Kirk KM, Larsen JT, Parker R, Petersen L, Jordan J, Kennedy M, Montgomery GW, Wade TD, Birgegård A, Lichtenstein P, Norring C, Landén M, Martin NG, Mortensen PB, Sullivan PF, Breen G, Bulik CM. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nature Genetics 2019, 51: 1207-1214. PMID: 31308545, PMCID: PMC6779477, DOI: 10.1038/s41588-019-0439-2.Peer-Reviewed Original ResearchGenome-wide association study implicates CHRNA2 in cannabis use disorder.
Demontis D, Rajagopal VM, Thorgeirsson TE, Als TD, Grove J, Leppälä K, Gudbjartsson DF, Pallesen J, Hjorthøj C, Reginsson GW, Tyrfingsson T, Runarsdottir V, Qvist P, Christensen JH, Bybjerg-Grauholm J, Bækvad-Hansen M, Huckins LM, Stahl EA, Timmermann A, Agerbo E, Hougaard DM, Werge T, Mors O, Mortensen PB, Nordentoft M, Daly MJ, Stefansson H, Stefansson K, Nyegaard M, Børglum AD. Genome-wide association study implicates CHRNA2 in cannabis use disorder. Nature Neuroscience 2019, 22: 1066-1074. PMID: 31209380, PMCID: PMC7596896, DOI: 10.1038/s41593-019-0416-1.Peer-Reviewed Original ResearchGene 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
2018
Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics.
Barbeira AN, Dickinson SP, Bonazzola R, Zheng J, Wheeler HE, Torres JM, Torstenson ES, Shah KP, Garcia T, Edwards TL, Stahl EA, Huckins LM, Nicolae DL, Cox NJ, Im HK. Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics. Nature Communications 2018, 9: 1825. PMID: 29739930, PMCID: PMC5940825, DOI: 10.1038/s41467-018-03621-1.Peer-Reviewed Original ResearchInvestigation of common, low-frequency and rare genome-wide variation in anorexia nervosa.
Huckins LM, Hatzikotoulas K, Southam L, Thornton LM, Steinberg J, Aguilera-McKay F, Treasure J, Schmidt U, Gunasinghe C, Romero A, Curtis C, Rhodes D, Moens J, Kalsi G, Dempster D, Leung R, Keohane A, Burghardt R, Ehrlich S, Hebebrand J, Hinney A, Ludolph A, Walton E, Deloukas P, Hofman A, Palotie A, Palta P, van Rooij FJA, Stirrups K, Adan R, Boni C, Cone R, Dedoussis G, van Furth E, Gonidakis F, Gorwood P, Hudson J, Kaprio J, Kas M, Keski-Rahkonen A, Kiezebrink K, Knudsen GP, Slof-Op 't Landt MCT, Maj M, Monteleone AM, Monteleone P, Raevuori AH, Reichborn-Kjennerud T, Tozzi F, Tsitsika A, van Elburg A, Collier DA, Sullivan PF, Breen G, Bulik CM, Zeggini E. Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa. Molecular Psychiatry 2018, 23: 1169-1180. PMID: 29155802, PMCID: PMC5828108, DOI: 10.1038/mp.2017.88.Peer-Reviewed Original ResearchRecent Genetics and Epigenetics Approaches to PTSD.
Daskalakis NP, Rijal CM, King C, Huckins LM, Ressler KJ. Recent Genetics and Epigenetics Approaches to PTSD. Current Psychiatry Reports 2018, 20: 30. PMID: 29623448, PMCID: PMC6486832, DOI: 10.1007/s11920-018-0898-7.Peer-Reviewed Original Research
2017
Linking cannabis use to depression and suicidal thoughts and behaviours.
Huckins LM. Linking cannabis use to depression and suicidal thoughts and behaviours. The Lancet. Psychiatry 2017, 4: 654-656. PMID: 28750822, DOI: 10.1016/S2215-0366(17)30311-5.Peer-Reviewed Original Research