2022
Genetic variants associated with psychiatric disorders are enriched at epigenetically active sites in lymphoid cells
Lynall ME, Soskic B, Hayhurst J, Schwartzentruber J, Levey DF, Pathak GA, Polimanti R, Gelernter J, Stein MB, Trynka G, Clatworthy MR, Bullmore E. Genetic variants associated with psychiatric disorders are enriched at epigenetically active sites in lymphoid cells. Nature Communications 2022, 13: 6102. PMID: 36243721, PMCID: PMC9569335, DOI: 10.1038/s41467-022-33885-7.Peer-Reviewed Original ResearchConceptsMultiple psychiatric disordersPsychiatric disordersPsychiatric risk variantT cellsLymphoid cellsRisk variantsImmune cell subsetsMental health disordersMultiple organ systemsAdaptive immune systemCell subsetsImmune cellsHealth disordersMyeloid cellsImmune systemBrain tissueOrgan systemsSpecific disordersDisordersPathogenesisAbnormalitiesGenetic variantsCellsCD4VariantsA Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program
Verma A, Tsao NL, Thomann LO, Ho YL, Iyengar SK, Luoh SW, Carr R, Crawford DC, Efird JT, Huffman JE, Hung A, Ivey KL, Levin MG, Lynch J, Natarajan P, Pyarajan S, Bick AG, Costa L, Genovese G, Hauger R, Madduri R, Pathak GA, Polimanti R, Voight B, Vujkovic M, Zekavat SM, Zhao H, Ritchie MD, Initiative V, Chang KM, Cho K, Casas JP, Tsao PS, Gaziano JM, O’Donnell C, Damrauer SM, Liao KP. A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program. PLOS Genetics 2022, 18: e1010113. PMID: 35482673, PMCID: PMC9049369, DOI: 10.1371/journal.pgen.1010113.Peer-Reviewed Original ResearchConceptsSevere COVID-19Million Veteran ProgramPhenome-wide association studyHost Genetics InitiativeGenetic architectureGenotype-phenotype dataAssociation studiesVeterans Affairs Million Veteran ProgramElectronic health record dataCOVID-19 severityHealth record dataCOVID-19Genetic variantsGenetics InitiativeABO locusPhenotypeVenous embolismCritical illnessDiseases codesMedical conditionsInternational ClassificationRecord dataStrong associationVeteran ProgramVariants
2021
ACE2 Netlas: In silico Functional Characterization and Drug-Gene Interactions of ACE2 Gene Network to Understand Its Potential Involvement in COVID-19 Susceptibility
Pathak GA, Wendt FR, Goswami A, Koller D, De Angelis F, Initiative C, Polimanti R. ACE2 Netlas: In silico Functional Characterization and Drug-Gene Interactions of ACE2 Gene Network to Understand Its Potential Involvement in COVID-19 Susceptibility. Frontiers In Genetics 2021, 12: 698033. PMID: 34512723, PMCID: PMC8429844, DOI: 10.3389/fgene.2021.698033.Peer-Reviewed Original ResearchGenome-wide association studiesGenetic variationFunctional characterizationCOVID-19 susceptibilityHuman genetic variationSilico functional characterizationDrug-gene interaction databaseTranscriptomic regulationGene networksGenetic variant associationsMetabolic domainsMulti-level characterizationPhenome-wide associationAssociation studiesDrug-gene interactionsVariant associationsInteraction databasesGenesKey adhesion moleculeGenetic variantsPhenotype categoriesPotential involvementMiRNAsAdhesion moleculesPotential mechanismsInvestigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder
Johnson EC, Kapoor M, Hatoum AS, Zhou H, Polimanti R, Wendt FR, Walters RK, Lai D, Kember RL, Hartz S, Meyers JL, Peterson RE, Ripke S, Bigdeli TB, Fanous AH, Pato CN, Pato MT, Goate AM, Kranzler HR, O'Donovan MC, Walters JTR, Gelernter J, Edenberg HJ, Agrawal A. Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder. Psychological Medicine 2021, 53: 1196-1204. PMID: 34231451, PMCID: PMC8738774, DOI: 10.1017/s003329172100266x.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significant single nucleotide polymorphismsLarge-scale genome-wide association studiesSignificant single nucleotide polymorphismsIndependent genome-wide significant single nucleotide polymorphismsSignificant genetic correlationsGenomic regionsSingle nucleotide polymorphismsGene expressionGenetic covariancePleiotropic associationsAssociation studiesGenetic correlationsGenetic variantsNucleotide polymorphismsGenetic overlapDisorder-specific effectsAlcohol use disorderGenetic influencesGenesUse disordersPleiotropic effects of telomere length loci with brain morphology and brain tissue expression
Pathak GA, Wendt FR, Levey DF, Mecca AP, van Dyck CH, Gelernter J, Polimanti R. Pleiotropic effects of telomere length loci with brain morphology and brain tissue expression. Human Molecular Genetics 2021, 30: 1360-1370. PMID: 33831179, PMCID: PMC8255129, DOI: 10.1093/hmg/ddab102.Peer-Reviewed Original ResearchConceptsMethylation expressionGenetic variantsMapping gene functionTelomere lengthChromatin associationChromatin profilesGene functionGenetic colocalizationGene mappingGenomic relationshipsNeuropsychiatric traitsPleiotropic rolesDrug-gene interactionsCertain lociBrain tissue expressionGenesLociPleiotropic effectsBrain morphology measuresNucleotide polymorphismsAncestry populationsTissue expressionPhenotypic associationsPleiotropyAncestry groups
2020
A large-scale genome-wide association study meta-analysis of cannabis use disorder
Johnson EC, Demontis D, Thorgeirsson TE, Walters RK, Polimanti R, Hatoum AS, Sanchez-Roige S, Paul SE, Wendt FR, Clarke TK, Lai D, Reginsson GW, Zhou H, He J, Baranger DAA, Gudbjartsson DF, Wedow R, Adkins DE, Adkins AE, Alexander J, Bacanu SA, Bigdeli TB, Boden J, Brown SA, Bucholz KK, Bybjerg-Grauholm J, Corley RP, Degenhardt L, Dick DM, Domingue BW, Fox L, Goate AM, Gordon SD, Hack LM, Hancock DB, Hartz SM, Hickie IB, Hougaard DM, Krauter K, Lind PA, McClintick JN, McQueen MB, Meyers JL, Montgomery GW, Mors O, Mortensen PB, Nordentoft M, Pearson JF, Peterson RE, Reynolds MD, Rice JP, Runarsdottir V, Saccone NL, Sherva R, Silberg JL, Tarter RE, Tyrfingsson T, Wall TL, Webb BT, Werge T, Wetherill L, Wright MJ, Zellers S, Adams MJ, Bierut LJ, Boardman JD, Copeland WE, Farrer LA, Foroud TM, Gillespie NA, Grucza RA, Harris KM, Heath AC, Hesselbrock V, Hewitt JK, Hopfer CJ, Horwood J, Iacono WG, Johnson EO, Kendler KS, Kennedy MA, Kranzler HR, Madden PAF, Maes HH, Maher BS, Martin NG, McGue M, McIntosh AM, Medland SE, Nelson EC, Porjesz B, Riley BP, Stallings MC, Vanyukov MM, Vrieze S, Workgroup P, Walters R, Polimanti R, Johnson E, McClintick J, Hatoum A, He J, Wendt F, Zhou H, Adams M, Adkins A, Aliev F, Bacanu S, Batzler A, Bertelsen S, Biernacka J, Bigdeli T, Chen L, Clarke T, Chou Y, Degenhardt F, Docherty A, Edwards A, Fontanillas P, Foo J, Fox L, Frank J, Giegling I, Gordon S, Hack L, Hartmann A, Hartz S, Heilmann-Heimbach S, Herms S, Hodgkinson C, Hoffman P, Hottenga J, Kennedy M, Alanne-Kinnunen M, Konte B, Lahti J, Lahti-Pulkkinen M, Lai D, Ligthart L, Loukola A, Maher B, Mbarek H, McIntosh A, McQueen M, Meyers J, Milaneschi Y, Palviainen T, Pearson J, Peterson R, Ripatti S, Ryu E, Saccone N, Salvatore J, Sanchez-Roige S, Schwandt M, Sherva R, Streit F, Strohmaier J, Thomas N, Wang J, Webb B, Wedow R, Wetherill L, Wills A, Boardman J, Chen D, Choi D, Copeland W, Culverhouse R, Dahmen N, Degenhardt L, Domingue B, Elson S, Frye M, Gäbel W, Hayward C, Ising M, Keyes M, Kiefer F, Kramer J, Kuperman S, Lucae S, Lynskey M, Maier W, Mann K, Männistö S, Müller-Myhsok B, Murray A, Nurnberger J, Palotie A, Preuss U, Räikkönen K, Reynolds M, Ridinger M, Scherbaum N, Schuckit M, Soyka M, Treutlein J, Witt S, Wodarz N, Zill P, Adkins D, Boden J, Boomsma D, Bierut L, Brown S, Bucholz K, Cichon S, Costello E, de Wit H, Diazgranados N, Dick D, Eriksson J, Farrer L, Foroud T, Gillespie N, Goate A, Goldman D, Grucza R, Hancock D, Harris K, Heath A, Hesselbrock V, Hewitt J, Hopfer C, Horwood J, Iacono W, Johnson E, Kaprio J, Karpyak V, Kendler K, Kranzler H, Krauter K, Lichtenstein P, Lind P, McGue M, MacKillop J, Madden P, Maes H, Magnusson P, Martin N, Medland S, Montgomery G, Nelson E, Nöthen M, Palmer A, Pederson N, Penninx B, Porjesz B, Rice J, Rietschel M, Riley B, Rose R, Rujescu D, Shen P, Silberg J, Stallings M, Tarter R, Vanyukov M, Vrieze S, Wall T, Whitfield J, Zhao H, Neale B, Gelernter J, Edenberg H, Agrawal A, Davis L, Bogdan R, Gelernter J, Edenberg H, Stefansson K, Børglum A, Agrawal A. A large-scale genome-wide association study meta-analysis of cannabis use disorder. The Lancet Psychiatry 2020, 7: 1032-1045. PMID: 33096046, PMCID: PMC7674631, DOI: 10.1016/s2215-0366(20)30339-4.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesGenome-wide significant lociLarge-scale genome-wide association studiesGenetic correlationsChromosome 7 locusTraits of interestLarge genome-wide association studiesLinkage disequilibrium score regressionChromosome 8 locusDifferent genetic underpinningsDifferent genetic correlationsWellcome Trust Case Control ConsortiumDisequilibrium score regressionNovel genetic variantsStrong genetic componentSignificant lociGenetic lociGenetic underpinningsGenetic componentLociScore regressionGenetic variantsGenetic overlapIntegrative sequencingGenetically-regulated transcriptomics & copy number variation of proctitis points to altered mitochondrial and DNA repair mechanisms in individuals of European ancestry
Pathak GA, Polimanti R, Silzer TK, Wendt FR, Chakraborty R, Phillips NR. Genetically-regulated transcriptomics & copy number variation of proctitis points to altered mitochondrial and DNA repair mechanisms in individuals of European ancestry. BMC Cancer 2020, 20: 954. PMID: 33008348, PMCID: PMC7530964, DOI: 10.1186/s12885-020-07457-1.Peer-Reviewed Original ResearchConceptsWhole blood tissuesCopy number variationsNumber variationsGene expressionGenome-Wide Human SNP Array 6.0Mitochondrial apoptosis regulationRNA-seq informationGenetic variantsDNA repair mechanismsGene expression changesDNA repair processesGene expression associationsGene expression profilesGene network informationDNA repair genesCopy number dataCopy number analysisGene OntologyApoptosis regulationDNA repairEnriched pathwaysEnriched processesOrganismal injuryTranscriptomic profilesExpression changes
2015
Nutritional habits, lifestyle, and genetic predisposition in cardiovascular and metabolic traits in Turkish population
Karaca S, Erge S, Cesuroglu T, Polimanti R. Nutritional habits, lifestyle, and genetic predisposition in cardiovascular and metabolic traits in Turkish population. Nutrition 2015, 32: 693-701. PMID: 26856649, DOI: 10.1016/j.nut.2015.12.027.Peer-Reviewed Original ResearchConceptsDietary habitsCausative relationshipGenetic predispositionTurkish populationDifferent cardiometabolic diseasesGenetic factorsCardiometabolic diseasesRisk factorsNutritional habitsDisease riskDifferent biological mechanismsMetabolic traitsSignificant correlationCausative networkGenetic variantsBiological mechanismsGenetic associationCMTPresent studyPredispositionLifestyleAnthropometric traitsHabitsPopulationFactors
2014
Human pharmacogenomic variation of antihypertensive drugs: from population genetics to personalized medicine
Polimanti R, Iorio A, Piacentini S, Manfellotto D, Fuciarelli M. Human pharmacogenomic variation of antihypertensive drugs: from population genetics to personalized medicine. Pharmacogenomics 2014, 15: 157-167. PMID: 24444406, DOI: 10.2217/pgs.13.231.Peer-Reviewed Original ResearchConceptsInterpopulation differencesNext-generation sequencing technologiesAntihypertensive drug responseFunctionality of genesPopulation geneticsGenetic variationSequencing technologiesDrug responseSilico analysisGeographic originPharmacogenomic variationGenetic variantsGeneticsRare variantsPharmacogenesPharmacogenetic variationVariantsGenesPersonalized medicineVariationImportant knowledgeStageGSTO1 uncommon genetic variants are associated with recurrent miscarriage risk
Polimanti R, Graziano ME, Lazzarin N, Vaquero E, Manfellotto D, Fuciarelli M. GSTO1 uncommon genetic variants are associated with recurrent miscarriage risk. Fertility And Sterility 2014, 101: 735-739. PMID: 24417908, DOI: 10.1016/j.fertnstert.2013.12.010.Peer-Reviewed Original ResearchConceptsRecurrent miscarriageUncommon genetic variantsGSTO1 geneRecurrent miscarriage riskGenetic variantsPhysiologic pregnancyPregnancy complicationsRisk factorsMiscarriage riskMAIN OUTCOMERM riskSignificant associationSingle nucleotide polymorphismsWomenK variantGenetic association studiesGSTO1Nucleotide polymorphismsRiskAssociation studiesDetoxification metabolismComplicationsPregnancyMiscarriagePathogenesis
2013
In silico investigation of the ATP7B gene: insights from functional prediction of non-synonymous substitution to protein structure
Squitti R, Siotto M, Bucossi S, Polimanti R. In silico investigation of the ATP7B gene: insights from functional prediction of non-synonymous substitution to protein structure. BioMetals 2013, 27: 53-64. PMID: 24253677, DOI: 10.1007/s10534-013-9686-3.Peer-Reviewed Original ResearchConceptsNon-synonymous substitutionsDisease-causing mutationsWilson disease-causing mutationsDisease-causing variantsUnknown gene variantsGenetic variantsProtein X-ray structuresSequence-based approachesCopper-transporting ATPaseNovel genetic variantsAmino acid changesUncharacterized proteinsProtein functionNovel ATP7B mutationsProtein domainsFunctional predictionCopper homeostasisBioinformatics methodsAmino acidic changeATP7B geneProtein structureAcid changesATP7B proteinGenesX-ray structureFunctional variation of the transthyretin gene among human populations and its correlation with amyloidosis phenotypes
Polimanti R, Di Girolamo M, Manfellotto D, Fuciarelli M. Functional variation of the transthyretin gene among human populations and its correlation with amyloidosis phenotypes. Amyloid 2013, 20: 256-262. PMID: 24111657, DOI: 10.3109/13506129.2013.844689.Peer-Reviewed Original ResearchConceptsHuman populationTTR-related amyloidosisCis-regulatory variantsGenetic variantsNon-coding variantsGenomes Project databaseAdditional genetic variantsDisease-causing mutationsGene functionTranscription factorsKb regionCardiac developmentSilico analysisFunctional variationTTR geneRegulatory functionsGenotype-phenotype correlationGenesFunctional impactDisease phenotypeNon-African individualsSignificant diversityMutationsPhenotypeTransthyretin gene
2012
Lack of Association Between Essential Hypertension and GSTO1 Uncommon Genetic Variants in Italian Patients
Polimanti R, Piacentini S, Lazzarin N, Re MA, Manfellotto D, Fuciarelli M. Lack of Association Between Essential Hypertension and GSTO1 Uncommon Genetic Variants in Italian Patients. Genetic Testing And Molecular Biomarkers 2012, 16: 615-620. PMID: 22283150, DOI: 10.1089/gtmb.2011.0310.Peer-Reviewed Original ResearchConceptsEssential hypertensionLack of associationEH patientsUncommon variantEH riskUncommon genetic variantsGlutathione S-transferaseGenetic variantsMale patientsHealthy controlsItalian patientsPatientsCommon polymorphismsStatistical significance levelSignificant outcomesFunctional effectsHypertensionPotential roleHaplotype investigationGenetic association analysis
2011
GSTO1*E155del polymorphism associated with increased risk for late-onset Alzheimer's disease: Association hypothesis for an uncommon genetic variant
Piacentini S, Polimanti R, Squitti R, Mariani S, Migliore S, Vernieri F, Rossini PM, Manfellotto D, Fuciarelli M. GSTO1*E155del polymorphism associated with increased risk for late-onset Alzheimer's disease: Association hypothesis for an uncommon genetic variant. Neuroscience Letters 2011, 506: 203-207. PMID: 22100662, DOI: 10.1016/j.neulet.2011.11.005.Peer-Reviewed Original ResearchConceptsUncommon genetic variantsGSTO1-1Genetic variantsClass genesGlutathione S-transferaseGenetic variationMultifunctional enzymeCellular detoxificationAlzheimer's diseaseGSTO2 genesGenetic linkageAllele-specific PCRS-transferaseChromosome 10qAD riskGene polymorphismsInterleukin-1β activationSpecific PCRPathophysiology of ADGenesLate-onset Alzheimer's diseasePolymorphismAD risk factorsOxidative stressPCR-RFLP