2024
Polygenic liability for anxiety in association with comorbid anxiety in multiple sclerosis
Kowalec K, Harder A, Dolovich C, Fitzgerald K, Salter A, Lu Y, Bernstein C, Bolton J, Cutter G, Fisk J, Gelernter J, Graff L, Hägg S, Hitchon C, Levey D, Lublin F, McKay K, Patten S, Patki A, Stein M, Tiwari H, Wolinsky J, Marrie R. Polygenic liability for anxiety in association with comorbid anxiety in multiple sclerosis. Annals Of Clinical And Translational Neurology 2024, 11: 1393-1404. PMID: 38715244, PMCID: PMC11187942, DOI: 10.1002/acn3.52025.Peer-Reviewed Original ResearchPolygenic scoresEuropean genetic ancestryUK BiobankAnxious symptomsIncreased oddsGenetic ancestrySelf-reported physician-diagnosedGenetic burdenComorbid anxietyGenome-wide association studiesCase-control designUnited States cohortDirection of effectAssociated with comorbid anxietyPhysician-diagnosedAssociated with disability progressionIndex diseaseStates cohortAnxiety symptomsMeta-analysesAssociation studiesSummary statisticsCurrent symptomsPolygenic liabilityRisk prediction
2023
Genetic Decomposition of the Heritable Component of Reported Childhood Maltreatment
Kuile A, Hübel C, Cheesman R, Coleman J, Peel A, Levey D, Stein M, Gelernter J, Rayner C, Eley T, Breen G. Genetic Decomposition of the Heritable Component of Reported Childhood Maltreatment. Biological Psychiatry Global Open Science 2023, 3: 716-724. PMID: 37881567, PMCID: PMC10593925, DOI: 10.1016/j.bpsgos.2023.03.003.Peer-Reviewed Original ResearchGenetic componentGenomic structural equationGenome-wide association study summary statisticsCommon genetic variantsResidual genetic varianceGeneral risk toleranceGenetic variancePutative traitsHeritable componentBehavioral traitsGenetic correlationsTraitsGenetic variantsHeritable characteristicsHeritable factorsHeritabilityEnvironmental factorsDecades of researchGenetic influencesSummary statisticsPhenotypeMultivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders
Hatoum A, Colbert S, Johnson E, Huggett S, Deak J, Pathak G, Jennings M, Paul S, Karcher N, Hansen I, Baranger D, Edwards A, Grotzinger A, Tucker-Drob E, Kranzler H, Davis L, Sanchez-Roige S, Polimanti R, Gelernter J, Edenberg H, Bogdan R, Agrawal A. Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders. Nature Mental Health 2023, 1: 210-223. PMID: 37250466, PMCID: PMC10217792, DOI: 10.1038/s44220-023-00034-y.Peer-Reviewed Original ResearchGenome-wide associationGenetic risk lociIndependent single nucleotide polymorphismsProblematic tobacco useSingle nucleotide polymorphismsRisk lociHigh polygenicityLociReceptor geneAddiction risk factorsPolygenic risk scoresEuropean descentPolygenicityGenesSummary statisticsSubstance use disordersSomatic conditionsAncestryRegulationConfersUse disordersPolymorphismGenetic liabilityDopamine regulationPDE4B
2019
A Putative Causal Relationship Between Genetically Determined Female Body Shape And Post-Traumatic Stress Disorder
Polimanti R, Amstadter A, Liberzon I, Nievergelt C, Workgroup P, Stein M, Koenen K, Gelernter J. A Putative Causal Relationship Between Genetically Determined Female Body Shape And Post-Traumatic Stress Disorder. European Neuropsychopharmacology 2019, 29: s751-s752. DOI: 10.1016/j.euroneuro.2017.06.094.Peer-Reviewed Original ResearchGenome-wide association studiesLarge genome-wide association studiesPutative causal relationshipAnthropometric traitsBody shapeEvolutionary mechanismsTop associationsAssociation studiesReproductive behaviorGenetic correlationsPleiotropic effectsGenetic overlapFemale body shapePolygenic score approachTraitsMendelian randomization analysisSummary statisticsRandomization analysisHuman sexual behaviorMechanism
2017
A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder
Polimanti R, Amstadter AB, Stein MB, Almli LM, Baker DG, Bierut LJ, Bradley B, Farrer LA, Johnson EO, King A, Kranzler HR, Maihofer AX, Rice JP, Roberts AL, Saccone NL, Zhao H, Liberzon I, Ressler KJ, Nievergelt CM, Koenen KC, Gelernter J, for The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup. A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder. Genome Medicine 2017, 9: 99. PMID: 29178946, PMCID: PMC5702961, DOI: 10.1186/s13073-017-0491-4.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesLarge genome-wide association studiesPutative causal relationshipAnthropometric traitsBody shapeEvolutionary mechanismsTop associationsAssociation studiesReproductive behaviorGenetic correlationsPleiotropic effectsGenetic overlapFemale body shapePolygenic score approachTraitsMendelian randomization analysisSummary statisticsRandomization analysisHuman sexual behaviorMechanismLargest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability
Duncan LE, Ratanatharathorn A, Aiello AE, Almli LM, Amstadter AB, Ashley-Koch AE, Baker DG, Beckham JC, Bierut LJ, Bisson J, Bradley B, Chen CY, Dalvie S, Farrer LA, Galea S, Garrett ME, Gelernter JE, Guffanti G, Hauser MA, Johnson EO, Kessler RC, Kimbrel NA, King A, Koen N, Kranzler HR, Logue MW, Maihofer AX, Martin AR, Miller MW, Morey RA, Nugent NR, Rice JP, Ripke S, Roberts AL, Saccone NL, Smoller JW, Stein DJ, Stein MB, Sumner JA, Uddin M, Ursano RJ, Wildman DE, Yehuda R, Zhao H, Daly MJ, Liberzon I, Ressler KJ, Nievergelt CM, Koenen KC. Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability. Molecular Psychiatry 2017, 23: 666-673. PMID: 28439101, PMCID: PMC5696105, DOI: 10.1038/mp.2017.77.Peer-Reviewed Original ResearchMeSH KeywordsAdultBipolar DisorderBlack or African AmericanCase-Control StudiesDepressive Disorder, MajorFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedMultifactorial InheritancePolymorphism, Single NucleotideRisk FactorsSchizophreniaSex CharacteristicsSex FactorsStress Disorders, Post-TraumaticWhite PeopleConceptsSingle nucleotide polymorphismsRisk lociSNP-level summary statisticsGenomic data resourcesGenome-wide significanceMolecular genetic dataComplex genetic disorderPolygenic risk predictionGenetic dataAncestral diversityLarge GWASGenetic indicesDiverse phenotypesGenetic riskHeritability estimatesLociSummary statisticsGenetic disordersHeritabilityGenetic influencesGWASDiversityPhenotypeTransethnicStrong evidenceWidespread signatures of positive selection in common risk alleles associated to autism spectrum disorder
Polimanti R, Gelernter J. Widespread signatures of positive selection in common risk alleles associated to autism spectrum disorder. PLOS Genetics 2017, 13: e1006618. PMID: 28187187, PMCID: PMC5328401, DOI: 10.1371/journal.pgen.1006618.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAttention Deficit Disorder with HyperactivityAutism Spectrum DisorderBipolar DisorderBrainComputational BiologyDepressive Disorder, MajorGene Expression ProfilingGene OntologyGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyGenomicsHumansPituitary GlandPolymorphism, Single NucleotideRisk FactorsSchizophreniaTranscriptomeConceptsPositive selectionGene Ontology enrichmentGene expression enrichmentPrevious genetic studiesGWAS summary statisticsNervous system developmentCommon risk allelesPsychiatric Genomics ConsortiumSystems geneticsOntology enrichmentRisk allelesSynapse organizationWidespread signaturesEvolutionary processesGenetic studiesGenomics ConsortiumGWASHuman evolutionAllelesIncomplete selectionEffect directionMinor alleleComplete selectionEnrichmentSummary statistics
2016
Genetic Relationship between Schizophrenia and Nicotine Dependence
Chen J, Bacanu SA, Yu H, Zhao Z, Jia P, Kendler KS, Kranzler HR, Gelernter J, Farrer L, Minica C, Pool R, Milaneschi Y, Boomsma DI, Penninx BW, Tyndale RF, Ware JJ, Vink JM, Kaprio J, Munafò M, Chen X. Genetic Relationship between Schizophrenia and Nicotine Dependence. Scientific Reports 2016, 6: 25671. PMID: 27164557, PMCID: PMC4862382, DOI: 10.1038/srep25671.Peer-Reviewed Original ResearchConceptsNeuroactive ligand-receptor interaction pathwayGenetic relationshipsEnergy production genesProtein modification genesLong non-coding RNAsNon-coding RNAsMultiple long non-coding RNAsProduction genesModification genesProtein geneInteraction pathwayGenesCalcium signalingP-value thresholdCritical roleRNANeuronal plasticityDifferent hypothesesFurther analysisLong-term potentiationSummary statisticsSignalingTraitsPathwayPlasticity