2025
Implications of gene Ă— environment interactions in post-traumatic stress disorder risk and treatment
Seah C, Sidamon-Eristoff A, Huckins L, Brennand K. Implications of gene Ă— environment interactions in post-traumatic stress disorder risk and treatment. Journal Of Clinical Investigation 2025, 135: e185102. PMID: 40026250, PMCID: PMC11870735, DOI: 10.1172/jci185102.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderGene x environment interactionsGenetic component of riskLimitations of genetic studiesTreating post-traumatic stress disorderExposure to traumatic stressPost-traumatic stress disorder riskInteraction of traumaGenetic screeningGenetic studiesGenetic componentEnvironment interactionMolecular mechanismsStress disorderPTSD riskTraumatic exposureTraumatic stressTraumatic experiencesDisorder riskGenetic factorsNovel therapeuticsBiological mechanismsGWASGeneral populationGenesHarnessing precision nutrition to individualize weight restoration in anorexia nervosa
Rodriguez I, Huckins L, Bulik C, Xu J, Igudesman D. Harnessing precision nutrition to individualize weight restoration in anorexia nervosa. Journal Of Eating Disorders 2025, 13: 29. PMID: 39962541, PMCID: PMC11834214, DOI: 10.1186/s40337-025-01209-x.Peer-Reviewed Original ResearchWeight restorationPrecision nutritionAnorexia nervosaGut microbiotaIndividualized nutrition therapyPsychiatric comorbiditiesHabitual lifestyle behaviorsPrecision nutrition approachesDuration of illnessRestore microbial diversityNutrition therapySevere psychiatric disordersNutrition prescriptionKeystone taxaDietary interventionGenetic markersMicrobial diversityWeight outcomesMetabolic profileEffective treatmentDietary planNutritional approachFecal energy lossPatient recoveryMortality rateGenetics of Anorexia Nervosa Translation to Future Personalized Therapies
Xu J, Igudesman D, Huckins L, Bulik C. Genetics of Anorexia Nervosa Translation to Future Personalized Therapies. Psychiatric Clinics Of North America 2025 DOI: 10.1016/j.psc.2025.01.007.Peer-Reviewed Original Research
2024
Evaluation of imputation performance of multiple reference panels in a Pakistani population
Xu J, Liu D, Hassan A, Genovese G, Cote A, Fennessy B, Cheng E, Charney A, Knowles J, Ayub M, Peterson R, Bigdeli T, Huckins L. Evaluation of imputation performance of multiple reference panels in a Pakistani population. Human Genetics And Genomics Advances 2024, 6: 100395. PMID: 39696820, PMCID: PMC11759560, DOI: 10.1016/j.xhgg.2024.100395.Peer-Reviewed Original ResearchGenome-wide association studiesReference panelImputation accuracyMultiple reference panelsPakistani individualsGenotype imputationAssociation studiesGenotype dataAncestry compositionEuropean individualsSample sizeTOPMedDiverse populationsPakistani populationImputationGenomeAncestryIndividualsGenotypesPopulationVariantsFuture panelsAuthor Correction: Modeling gene Ă— environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression
Seah C, Breen M, Rusielewicz T, Bader H, Xu C, Hunter C, McCarthy B, Deans P, Chattopadhyay M, Goldberg J, Dobariya S, Desarnaud F, Makotkine I, Flory J, Bierer L, Staniskyte M, Noggle S, Huckins L, Paull D, Brennand K, Yehuda R. Author Correction: Modeling gene Ă— environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression. Nature Neuroscience 2024, 28: 214-214. PMID: 39633181, PMCID: PMC11706769, DOI: 10.1038/s41593-024-01854-6.Peer-Reviewed Original ResearchChronic overlapping pain conditions and nociplastic pain
Johnston K, Signer R, Huckins L. Chronic overlapping pain conditions and nociplastic pain. Human Genetics And Genomics Advances 2024, 6: 100381. PMID: 39497418, PMCID: PMC11617767, DOI: 10.1016/j.xhgg.2024.100381.Peer-Reviewed Original ResearchGenome wide association studiesTranscriptome-wide associationChronic overlapping pain conditionsTissue enrichment analysisSingle nucleotide polymorphismsEnrichment analysisNociplastic painPain conditionsIndependent single nucleotide polymorphismsMultisite chronic painGene set enrichment analysisSNP heritabilityUnique genesNeuropathic pain phenotypesAssociation studiesPolygenic traitChronic pain conditionsGene setsNucleotide polymorphismsMetabolic traitsHeritable traitGenetic overlapPain phenotypesPain descriptorsPain experience42. STRESS EXPOSURE DYNAMICALLY REGULATES EQTL ACTIVITY IN THE POST-MORTEM BRAIN AND IN HIPSC-DERIVED NEURONS
Seah C, Signer R, Young H, Hicks E, Rusielewicz T, Bader H, Xu C, Breen M, Paull D, Yehuda R, Girgenti M, Brennand K, Huckins L. 42. STRESS EXPOSURE DYNAMICALLY REGULATES EQTL ACTIVITY IN THE POST-MORTEM BRAIN AND IN HIPSC-DERIVED NEURONS. European Neuropsychopharmacology 2024, 87: 71-72. DOI: 10.1016/j.euroneuro.2024.08.156.Peer-Reviewed Original ResearchPost-mortem brainsTranscription factor binding sitesAbsence of cellular stressCombat-exposed veteransFactor binding sitesImpact gene expressionBinding sitesGR binding sitesPositive regulatory activityMotif enrichmentSequence readsCRISPRi screenOpen chromatinFunctional annotationBrain regionsTraumatic stressCRISPR screensEQTLTraumatic experiencesLeading locusPTSDPerturbed genesRegulatory architectureTranscriptomic activityTranscriptomic responseW22. 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 expression23. GENOME-WIDE ASSOCIATION STUDIES OF BINGE-EATING BEHAVIOUR AND ANOREXIA NERVOSA YIELD INSIGHTS INTO THE UNIQUE AND SHARED BIOLOGY OF EATING DISORDER PHENOTYPES
Huckins L, Termorshuizen J, Davies H, Lee S, Johnson J, Munn-Chernoff M, Thornton L, Källberg J, Bulik C, Breen G, Coleman J. 23. GENOME-WIDE ASSOCIATION STUDIES OF BINGE-EATING BEHAVIOUR AND ANOREXIA NERVOSA YIELD INSIGHTS INTO THE UNIQUE AND SHARED BIOLOGY OF EATING DISORDER PHENOTYPES. European Neuropsychopharmacology 2024, 87: 60. DOI: 10.1016/j.euroneuro.2024.08.137.Peer-Reviewed Original ResearchGenome-wide association studiesIdentification of novel lociGenome-wide association study meta-analysisGenetic correlationsEating Disorders Working GroupBinge-eating behaviorNovel lociGenome-wideGenomic lociAssociation studiesLociGenetic componentEating disorder phenotypesPhenotypeEarly onset obesityBE phenotypeSevere early onset obesityDisorder phenotypesTrans-diagnosticAN subtypesAN-BPAN-RAN-R.Eating disordersBinge-eating/purgingOral Contraceptives and the Risk of Psychiatric Side Effects: A Review
Ciarcia J, Huckins L. Oral Contraceptives and the Risk of Psychiatric Side Effects: A Review. Complex Psychiatry 2024, 10: 36-44. PMID: 39148498, PMCID: PMC11324216, DOI: 10.1159/000539515.Peer-Reviewed Original ResearchMood-related side effectsPsychiatric side effectsPsychiatric riskOral contraceptivesSide effectsSymptoms of depressionPrescription psychotropic medicationsOC usersMood side effectsSide effects of oral contraceptivesEffects of oral contraceptivesMood symptomsRisks of oral contraceptivesOC treatmentPsychotropic medicationsMood improvementPsychiatric disordersEating disordersProgestin-only pillsSubgroups of usersPlacebo usersRandomized controlled trialsCombination pillMoodClinical significanceWhat Next for Eating Disorder Genetics? Replacing Myths With Facts to Sharpen Our Understanding
Huckins L, Signer R, Johnson J, Wu Y, Mitchell K, Bulik C. What Next for Eating Disorder Genetics? Replacing Myths With Facts to Sharpen Our Understanding. FOCUS The Journal Of Lifelong Learning In Psychiatry 2024, 22: 418-429. PMID: 38988461, PMCID: PMC11231467, DOI: 10.1176/appi.focus.24022014.Peer-Reviewed Original ResearchShared Genetic Architecture Between Schizophrenia and Anorexia Nervosa: A Cross-trait Genome-Wide Analysis
Lu Z, Ploner A, BirgegĂĄrd A, Adan R, Alfredsson L, Ando T, Andreassen O, Baker J, Bergen A, Berrettini W, BirgegĂĄrd A, Boden J, Boehm I, Perica V, Brandt H, Breen G, Bryois J, Buehren K, Bulik C, Burghardt R, Cassina M, Cichon S, Coleman J, Cone R, Courtet P, Crawford S, Crow S, Crowley J, Danner U, Davis O, de Zwaan M, Dedoussis G, DeSocio J, Dick D, Dikeos D, Dina C, Dmitrzak-Weglarz M, Docampo E, Duncan L, Egberts K, Ehrlich S, EscaramĂs G, Esko T, Estivill X, Farmer A, Favaro A, Fernández-Aranda F, Fischer K, Föcker M, Foretova L, Forstner A, Forzan M, Franklin C, Gallinger S, Giegling I, Giusti-RodrĂguez P, Gonidakis F, Gordon S, Gorwood P, Mayora M, Grove J, Guillaume S, Guo Y, Hakonarson H, Halmi K, Hanscombe K, Hatzikotoulas K, Hauser J, Hebebrand J, Helder S, Herms S, Herpertz-Dahlmann B, Herzog W, Hinney A, Horwood L, HĂĽbel C, Huckins L, Hudson J, Imgart H, Inoko H, Janout V, JimĂ©nez-Murcia S, Johnson C, Jordan J, JuliĂ A, Kalsi G, Kaminská D, Kaplan A, Kaprio J, Karhunen L, Karwautz A, Kas M, Kaye W, Kennedy J, Kennedy M, Keski-Rahkonen A, Kiezebrink K, Kim Y, Klareskog L, Klump K, LandĂ©n M, Larsen J, Le Hellard S, Leppä V, Li D, Lichtenstein P, Lilenfeld L, Lin B, Lissowska J, Luykx J, Maj M, Marsal S, Martin N, Mattheisen M, Mattingsdal M, Medland S, Metspalu A, Meulenbelt I, Micali N, Mitchell K, Mitchell J, Monteleone A, Monteleone P, Mortensen P, Munn-Chernoff M, Nacmias B, Navratilova M, Ntalla I, Olsen C, Ophoff R, Padyukov L, Pantel J, Papezova H, Parker R, Pearson J, Pedersen N, Petersen L, Pinto D, Purves K, Raevuori A, Ramoz N, Reichborn-Kjennerud T, Ricca V, Ripatti S, Ripke S, Ritschel F, Roberts M, Rujescu D, Rybakowski F, Santonastaso P, Scherag A, Scherer S, Schmidt U, Schork N, Schosser A, Seitz J, Slachtova L, Slagboom P, Landt M, Slopien A, Sorbi S, Strober M, Sullivan P, ĹšwiÄ…tkowska B, Szatkiewicz J, Tenconi E, Thornton L, Tortorella A, Treasure J, Tsitsika A, Tyszkiewicz-Nwafor M, van Elburg A, van Furth E, Wade T, Wagner G, Watson H, Werge T, Whiteman D, Widen E, Woodside D, Yao S, Yilmaz Z, Zeggini E, Zerwas S, Zipfel S, Breen G, Bulik C, Bulik C, Bergen S. Shared Genetic Architecture Between Schizophrenia and Anorexia Nervosa: A Cross-trait Genome-Wide Analysis. Schizophrenia Bulletin 2024, 50: 1255-1265. PMID: 38848516, PMCID: PMC11349005, DOI: 10.1093/schbul/sbae087.Peer-Reviewed Original ResearchPolygenic overlapConditional/conjunctional false discovery rateGenome-wide association studiesGenome-wide analysisConcordant effect directionsProportion of variantsNovel lociFalse discovery rateFunctional annotationGenetic architectureGenetic enrichmentAssociation studiesMultiple genesSynapse organizationMendelian randomization analysisGenetic associationCo-aggregationLociGenetic componentGenetic etiologyAnorexia nervosaFamilial co-aggregationDiscovery rateGenetic factorsRandomization analysisComorbidity Profiles of Posttraumatic Stress Disorder Across the Medical Phenome
Hicks E, Niarchou M, Goleva S, Kabir D, Johnson J, Johnston K, Ciarcia J, Pathak G, Smoller J, Davis L, Nievergelt C, Koenen K, Huckins L, Choi K, Group P. Comorbidity Profiles of Posttraumatic Stress Disorder Across the Medical Phenome. Biological Psychiatry Global Open Science 2024, 4: 100337. PMID: 39050781, PMCID: PMC11268109, DOI: 10.1016/j.bpsgos.2024.100337.Peer-Reviewed Original ResearchElectronic health recordsClinical knowledge gapsPhysical health problemsPhenome-wide associationPheWAS analysisBiobank participantsHealth recordsEpidemiological researchHealthcare systemTest associationsMedical phenomeAssociated with osteoporosisPulmonary heart diseasePhecodesHealth problemsLogistic regressionPosttraumatic stress disorderSex differencesPheWASComorbidity profilesHeart diseaseStress disorderInteraction termsAssociationPTSDCritical reasoning on the co-expression module QTL in the dorsolateral prefrontal cortex
Cote A, Young H, Huckins L. Critical reasoning on the co-expression module QTL in the dorsolateral prefrontal cortex. Human Genetics And Genomics Advances 2024, 5: 100311. PMID: 38773772, PMCID: PMC11214266, DOI: 10.1016/j.xhgg.2024.100311.Peer-Reviewed Original ResearchConceptsExpression quantitative trait lociGene co-expressionCo-expressionExpression quantitative trait locus methodGenetic variantsComplex trait heritabilityMultiple testing burdenGene-based testsQuantitative trait lociTrans-eQTLsCis-eQTLsRegulatory variationSequencing datasetsTrait lociGene regulationTrait heritabilityGene functionGene modulesReal-data applicationModule genesGenesTesting burdenDorsolateral prefrontal cortexVariantsComparison to prior studiesGenome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder
Nievergelt C, Maihofer A, Atkinson E, Chen C, Choi K, Coleman J, Daskalakis N, Duncan L, Polimanti R, Aaronson C, Amstadter A, Andersen S, Andreassen O, Arbisi P, Ashley-Koch A, Austin S, Avdibegoviç E, Babić D, Bacanu S, Baker D, Batzler A, Beckham J, Belangero S, Benjet C, Bergner C, Bierer L, Biernacka J, Bierut L, Bisson J, Boks M, Bolger E, Brandolino A, Breen G, Bressan R, Bryant R, Bustamante A, Bybjerg-Grauholm J, Bækvad-Hansen M, Børglum A, Børte S, Cahn L, Calabrese J, Caldas-de-Almeida J, Chatzinakos C, Cheema S, Clouston S, Colodro-Conde L, Coombes B, Cruz-Fuentes C, Dale A, Dalvie S, Davis L, Deckert J, Delahanty D, Dennis M, Desarnaud F, DiPietro C, Disner S, Docherty A, Domschke K, Dyb G, Kulenović A, Edenberg H, Evans A, Fabbri C, Fani N, Farrer L, Feder A, Feeny N, Flory J, Forbes D, Franz C, Galea S, Garrett M, Gelaye B, Gelernter J, Geuze E, Gillespie C, Goleva S, Gordon S, Goçi A, Grasser L, Guindalini C, Haas M, Hagenaars S, Hauser M, Heath A, Hemmings S, Hesselbrock V, Hickie I, Hogan K, Hougaard D, Huang H, Huckins L, Hveem K, Jakovljević M, Javanbakht A, Jenkins G, Johnson J, Jones I, Jovanovic T, Karstoft K, Kaufman M, Kennedy J, Kessler R, Khan A, Kimbrel N, King A, Koen N, Kotov R, Kranzler H, Krebs K, Kremen W, Kuan P, Lawford B, Lebois L, Lehto K, Levey D, Lewis C, Liberzon I, Linnstaedt S, Logue M, Lori A, Lu Y, Luft B, Lupton M, Luykx J, Makotkine I, Maples-Keller J, Marchese S, Marmar C, Martin N, MartĂnez-Levy G, McAloney K, McFarlane A, McLaughlin K, McLean S, Medland S, Mehta D, Meyers J, Michopoulos V, Mikita E, Milani L, Milberg W, Miller M, Morey R, Morris C, Mors O, Mortensen P, Mufford M, Nelson E, Nordentoft M, Norman S, Nugent N, O’Donnell M, Orcutt H, Pan P, Panizzon M, Pathak G, Peters E, Peterson A, Peverill M, Pietrzak R, Polusny M, Porjesz B, Powers A, Qin X, Ratanatharathorn A, Risbrough V, Roberts A, Rothbaum A, Rothbaum B, Roy-Byrne P, Ruggiero K, Rung A, Runz H, Rutten B, de Viteri S, Salum G, Sampson L, Sanchez S, Santoro M, Seah C, Seedat S, Seng J, Shabalin A, Sheerin C, Silove D, Smith A, Smoller J, Sponheim S, Stein D, Stensland S, Stevens J, Sumner J, Teicher M, Thompson W, Tiwari A, Trapido E, Uddin M, Ursano R, ValdimarsdĂłttir U, Van Hooff M, Vermetten E, Vinkers C, Voisey J, Wang Y, Wang Z, Waszczuk M, Weber H, Wendt F, Werge T, Williams M, Williamson D, Winsvold B, Winternitz S, Wolf C, Wolf E, Xia Y, Xiong Y, Yehuda R, Young K, Young R, Zai C, Zai G, Zervas M, Zhao H, Zoellner L, Zwart J, deRoon-Cassini T, van Rooij S, van den Heuvel L, Stein M, Ressler K, Koenen K. Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder. Nature Genetics 2024, 56: 792-808. PMID: 38637617, PMCID: PMC11396662, DOI: 10.1038/s41588-024-01707-9.Peer-Reviewed Original ResearchConceptsMeta-analysis of genome-wide association studiesGenome-wide significant lociMulti-ancestry meta-analysisGenome-wide association analysisGenome-wide association studiesIndividuals of European ancestryPotential causal genesNative American ancestryMulti-omics approachPost-traumatic stress disorderAdmixed individualsSignificant lociRisk lociCausal genesAssociation studiesAssociation analysisFunctional genesTranscription factorsGenetic studiesAmerican ancestryEuropean ancestryAxon guidanceSynaptic structureLociGenes209 Transcriptomic Analysis of the Post-mortem Brain in Intracranial Atherosclerosis Implicates Interferon Signaling
Seah C, Devarajan A, Jurczyszak D, Chakka A, Huckins L, Brennand K, Girgenti M. 209 Transcriptomic Analysis of the Post-mortem Brain in Intracranial Atherosclerosis Implicates Interferon Signaling. Neurosurgery 2024, 70: 55-56. DOI: 10.1227/neu.0000000000002809_209.Peer-Reviewed Original ResearchIntracranial atherosclerotic stenosisIntracranial arteriesInterferon-inducible genesInterferon signalingPeripheral atherosclerosisCerebral atherosclerosisExpression of interferon-inducible genesGlial cellsSymptomatic intracranial atherosclerotic stenosisInduced pluripotent stem cellsPost-mortem brainsWorsened functional outcomesHuman induced pluripotent stem cellsUpregulation of interferon inducible genesCause of ischemic strokePluripotent stem cellsRisk of atherosclerosisLipid-rich plaquesRisk factor managementClinical outcomesPoor prognosisExcitatory neuronsIncreased morbidityHistopathological profileFunctional outcomesDissecting the biology of feeding and eating disorders
Huckins L, Brennand K, Bulik C. Dissecting the biology of feeding and eating disorders. Trends In Molecular Medicine 2024, 30: 380-391. PMID: 38431502, DOI: 10.1016/j.molmed.2024.01.009.Peer-Reviewed Original ResearchGenome-wide association studiesVariants to genesGenes to pathwaysSignificant lociFunctional genomicsAssociation studiesGenetic relationshipsIntestinal microbiotaGenetic researchGenomeGenetic correlationsGenesMetabolic contributorsAnorexia nervosaEating disordersPathwayBiologyMetabolic outcomesRisk factorsLociMicrobiotaPhenomicsLethal illnessTraitsFeedingGenomic insights into the comorbidity between type 2 diabetes and schizophrenia
Arruda A, Khandaker G, Morris A, Smith G, Huckins L, Zeggini E. Genomic insights into the comorbidity between type 2 diabetes and schizophrenia. Schizophrenia 2024, 10: 22. PMID: 38383672, PMCID: PMC10881980, DOI: 10.1038/s41537-024-00445-5.Peer-Reviewed Original ResearchBody mass indexType 2 diabetesType 2 diabetes riskEffect of body mass indexPutative effector genesN-methyl-D-aspartatePublic health challengeIncreased body mass indexLipid-related pathwaysRisk-increasing effectMulti-omics dataMendelian randomizationPotential causal relationshipGene expression studiesDirection of effectMental healthDrug repurposing opportunitiesAssociation signalsGenomic lociGenomic insightsHealth challengesEffector genesGenetic liabilityMass indexExpression studies
2023
Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals
Zhou H, Kember R, Deak J, Xu H, Toikumo S, Yuan K, Lind P, Farajzadeh L, Wang L, Hatoum A, Johnson J, Lee H, Mallard T, Xu J, Johnston K, Johnson E, Nielsen T, Galimberti M, Dao C, Levey D, Overstreet C, Byrne E, Gillespie N, Gordon S, Hickie I, Whitfield J, Xu K, Zhao H, Huckins L, Davis L, Sanchez-Roige S, Madden P, Heath A, Medland S, Martin N, Ge T, Smoller J, Hougaard D, Børglum A, Demontis D, Krystal J, Gaziano J, Edenberg H, Agrawal A, Justice A, Stein M, Kranzler H, Gelernter J. Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals. Nature Medicine 2023, 29: 3184-3192. PMID: 38062264, PMCID: PMC10719093, DOI: 10.1038/s41591-023-02653-5.Peer-Reviewed Original ResearchEating disorders: are gut microbiota to blame?
Xu J, Carroll I, Huckins L. Eating disorders: are gut microbiota to blame? Trends In Molecular Medicine 2023, 30: 317-320. PMID: 38040602, PMCID: PMC11009075, DOI: 10.1016/j.molmed.2023.11.007.Peer-Reviewed Original Research
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