2021
The integration of genetically-regulated transcriptomics and electronic health records highlights a pattern of medical outcomes related to increased hepatic transthyretin expression
Pathak GA, De Lillo A, Wendt FR, De Angelis F, Koller D, Mendoza B, Jacoby D, Miller EJ, Buxbaum JN, Polimanti R. The integration of genetically-regulated transcriptomics and electronic health records highlights a pattern of medical outcomes related to increased hepatic transthyretin expression. Amyloid 2021, 29: 110-119. PMID: 34935565, PMCID: PMC9213571, DOI: 10.1080/13506129.2021.2018678.Peer-Reviewed Original ResearchConceptsGenotype-Tissue Expression (GTEx) projectMulti-tissue analysisElectronic health recordsTTR amyloid formationGenetic regulationExpression projectRNA interferenceTranscriptomic profilesGene expressionExpression informationHepatic expressionHealth outcomesPhenotypic informationAmyloid formationHealth recordsCarpal tunnel syndromeTranscriptionTransthyretin expressionSystemic amyloidosesHepatic transcriptionPathological processesExpressionTunnel syndromeGastrointestinal diseasesSurgical proceduresInvestigation 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 disordersBi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions
Levey DF, Stein MB, Wendt FR, Pathak GA, Zhou H, Aslan M, Quaden R, Harrington KM, Nuñez YZ, Overstreet C, Radhakrishnan K, Sanacora G, McIntosh AM, Shi J, Shringarpure SS, Concato J, Polimanti R, Gelernter J. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nature Neuroscience 2021, 24: 954-963. PMID: 34045744, PMCID: PMC8404304, DOI: 10.1038/s41593-021-00860-2.Peer-Reviewed Original ResearchConceptsTranscriptome-wide association studyMillion Veteran ProgramTranscriptome-wide association study (TWAS) analysisGenomic risk lociComplex psychiatric traitsGenetic architectureRisk lociGene expressionAssociation studiesLikely pathogenicityPsychiatric traitsVeteran ProgramNew therapeutic directionEuropean ancestryNew insightsAncestryUK BiobankAfrican ancestrySubstantial replicationExpressionLarge independent cohortsGWASTherapeutic directionsGenesLoci
2020
Genetically-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 changesReproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program
Levey DF, Gelernter J, Polimanti R, Zhou H, Cheng Z, Aslan M, Quaden R, Concato J, Radhakrishnan K, Bryois J, Sullivan PF, Stein M. Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program. American Journal Of Psychiatry 2020, 177: 223-232. PMID: 31906708, PMCID: PMC7869502, DOI: 10.1176/appi.ajp.2019.19030256.Peer-Reviewed Original ResearchConceptsNovel genome-wide significant associationsGene expressionGenome-wide significant signalsGenome-wide significant associationMillion Veteran ProgramWide association studyGenetic risk lociSignificant genetic correlationsGenetic risk mechanismsGenetic architectureGlobal regulatorChromosome 3Risk lociChromosome 6Chromosome 7Association studiesLargest GWASLarge biobanksGlobal regulationGenetic correlationsContinuous traitsVeteran ProgramGWASsLociPrevious GWASs