2025
Revealing secrets of human genetic variation with population databases
Lake N. Revealing secrets of human genetic variation with population databases. Nature Reviews Genetics 2025, 26: 377-377. PMID: 40316690, DOI: 10.1038/s41576-025-00848-9.Peer-Reviewed Original Research
2024
Prioritizing disease-related rare variants by integrating gene expression data
Guo H, Urban A, Wong H. Prioritizing disease-related rare variants by integrating gene expression data. PLOS Genetics 2024, 20: e1011412. PMID: 39348415, PMCID: PMC11466430, DOI: 10.1371/journal.pgen.1011412.Peer-Reviewed Original ResearchConceptsGene expression dataRare variantsExpression dataRare variant association methodsExcess of rare variantsImpact of rare variantsContext of human diseaseHuman genetic variationGenetic variationGene expressionComplex diseasesHuman diseasesGenesMolecular mechanismsFunctional consequencesRare variant typesAlzheimer's diseaseVariant typeVariantsAssociation methodStatistical frameworkSimulation studySample sizeOmicsAlzheimerDetection and analysis of complex structural variation in human genomes across populations and in brains of donors with psychiatric disorders
Zhou B, Arthur J, Guo H, Kim T, Huang Y, Pattni R, Wang T, Kundu S, Luo J, Lee H, Nachun D, Purmann C, Monte E, Weimer A, Qu P, Shi M, Jiang L, Yang X, Fullard J, Bendl J, Girdhar K, Kim M, Chen X, Consortium P, Greenleaf W, Duncan L, Ji H, Zhu X, Song G, Montgomery S, Palejev D, Dohna H, Roussos P, Kundaje A, Hallmayer J, Snyder M, Wong H, Urban A. Detection and analysis of complex structural variation in human genomes across populations and in brains of donors with psychiatric disorders. Cell 2024, 187: 6687-6706.e25. PMID: 39353437, PMCID: PMC11608572, DOI: 10.1016/j.cell.2024.09.014.Peer-Reviewed Original ResearchComplex structural variationsNatural human genetic variationHuman genetic variationCell type-specific expressionHuman-specific evolutionDifferential gene expressionStructural variationsContinental populationsChromatin accessibilityHuman genomeGenetic variationNeural genesGenomeGene expressionRisk allelesMolecular etiologyCell typesGenesPostmortem brainsChromatinLociAllelesMachine-learning-based methodsMultiomicsBrain regionsEmbracing cancer complexity: Hallmarks of systemic disease
Swanton C, Bernard E, Abbosh C, André F, Auwerx J, Balmain A, Bar-Sagi D, Bernards R, Bullman S, DeGregori J, Elliott C, Erez A, Evan G, Febbraio M, Hidalgo A, Jamal-Hanjani M, Joyce J, Kaiser M, Lamia K, Locasale J, Loi S, Malanchi I, Merad M, Musgrave K, Patel K, Quezada S, Wargo J, Weeraratna A, White E, Winkler F, Wood J, Vousden K, Hanahan D. Embracing cancer complexity: Hallmarks of systemic disease. Cell 2024, 187: 1589-1616. PMID: 38552609, PMCID: PMC12077170, DOI: 10.1016/j.cell.2024.02.009.Peer-Reviewed Original ResearchConceptsHuman genetic variationSystemic diseaseHallmarks of cancerTumor-related thrombosisGenetic variationGene-environment interactionsCancer-related deathsComplexity of cancerMolecular basisTreat human cancersNervous system interactionsMechanisms of carcinogenesisHuman cancersImprove patient qualityCancer cachexiaSystemic manifestationsTumor micro-Cancer outcomesDistant organsTumor initiationMolecular oncologyTumorPatients' qualityPrevent cancerCancerGenome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever
Kotliar D, Raju S, Tabrizi S, Odia I, Goba A, Momoh M, Sandi J, Nair P, Phelan E, Tariyal R, Eromon P, Mehta S, Robles-Sikisaka R, Siddle K, Stremlau M, Jalloh S, Gire S, Winnicki S, Chak B, Schaffner S, Pauthner M, Karlsson E, Chapin S, Kennedy S, Branco L, Kanneh L, Vitti J, Broodie N, Gladden-Young A, Omoniwa O, Jiang P, Yozwiak N, Heuklom S, Moses L, Akpede G, Asogun D, Rubins K, Kales S, Happi A, Iruolagbe C, Dic-Ijiewere M, Iraoyah K, Osazuwa O, Okonkwo A, Kunz S, McCormick J, Khan S, Honko A, Lander E, Oldstone M, Hensley L, Folarin O, Okogbenin S, Günther S, Ollila H, Tewhey R, Okokhere P, Schieffelin J, Andersen K, Reilly S, Grant D, Garry R, Barnes K, Happi C, Sabeti P. Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever. Nature Microbiology 2024, 9: 751-762. PMID: 38326571, PMCID: PMC10914620, DOI: 10.1038/s41564-023-01589-3.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesSignatures of positive selectionHuman genetic variationFatal outcomeNigerian cohortLassa feverLassa virusFunctional characterization assaysVariant associationsGenetic variationHuman leukocyte antigen typingPositive selectionAssociated with decreased riskSevere Lassa feverCases of Lassa feverViral pathogenesisEntry factorsLASV infectionCharacterization assaysMild symptomsFeverAntigenic typesSeroprevalence surveyCohort
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 mechanisms
2019
Multi-platform discovery of haplotype-resolved structural variation in human genomes
Chaisson MJP, Sanders AD, Zhao X, Malhotra A, Porubsky D, Rausch T, Gardner EJ, Rodriguez OL, Guo L, Collins RL, Fan X, Wen J, Handsaker RE, Fairley S, Kronenberg ZN, Kong X, Hormozdiari F, Lee D, Wenger AM, Hastie AR, Antaki D, Anantharaman T, Audano PA, Brand H, Cantsilieris S, Cao H, Cerveira E, Chen C, Chen X, Chin CS, Chong Z, Chuang NT, Lambert CC, Church DM, Clarke L, Farrell A, Flores J, Galeev T, Gorkin DU, Gujral M, Guryev V, Heaton WH, Korlach J, Kumar S, Kwon JY, Lam ET, Lee JE, Lee J, Lee WP, Lee SP, Li S, Marks P, Viaud-Martinez K, Meiers S, Munson KM, Navarro FCP, Nelson BJ, Nodzak C, Noor A, Kyriazopoulou-Panagiotopoulou S, Pang AWC, Qiu Y, Rosanio G, Ryan M, Stütz A, Spierings DCJ, Ward A, Welch AE, Xiao M, Xu W, Zhang C, Zhu Q, Zheng-Bradley X, Lowy E, Yakneen S, McCarroll S, Jun G, Ding L, Koh CL, Ren B, Flicek P, Chen K, Gerstein MB, Kwok PY, Lansdorp PM, Marth GT, Sebat J, Shi X, Bashir A, Ye K, Devine SE, Talkowski ME, Mills RE, Marschall T, Korbel JO, Eichler EE, Lee C. Multi-platform discovery of haplotype-resolved structural variation in human genomes. Nature Communications 2019, 10: 1784. PMID: 30992455, PMCID: PMC6467913, DOI: 10.1038/s41467-018-08148-z.Peer-Reviewed Original ResearchConceptsStructural variantsSequencing studiesHigh-throughput sequencing studiesHuman genetic diversityHuman genetic variationGenome sequencing studiesGenetic diversityHuman genomeGenetic variationSequencing technologiesGenome ProjectSV detectionGenomeIndel variantsSV callsetsStructural variationsRecurrent microdeletionsDisease associationsMicroduplication syndromesOptical mappingVariantsSevenfold increaseDiversityCritical regionCallsets
2017
The Role of the Endocannabinoid System and Genetic Variation in Adolescent Brain Development
Meyer HC, Lee FS, Gee DG. The Role of the Endocannabinoid System and Genetic Variation in Adolescent Brain Development. Neuropsychopharmacology 2017, 43: 21-33. PMID: 28685756, PMCID: PMC5719094, DOI: 10.1038/npp.2017.143.Peer-Reviewed Original ResearchConceptsAnxiety-related behaviorDevelopmental trajectoriesAdolescent brain developmentRegulation of fearConsequences of stressGenetic variationBrain developmentBehavioral processingECB systemPrefrontal cortexEmotional behaviorHuman genetic variationCorticolimbic structuresStress responsivityBrain regionsAdolescenceRegulation of stressNeural circuitsEndocannabinoid systemAnxietyEnvironmental perturbationsRole of eCBFunctional implicationsCentral roleLife spanNovel determinants of mammalian primary microRNA processing revealed by systematic evaluation of hairpin-containing transcripts and human genetic variation
Roden C, Gaillard J, Kanoria S, Rennie W, Barish S, Cheng J, Pan W, Liu J, Cotsapas C, Ding Y, Lu J. Novel determinants of mammalian primary microRNA processing revealed by systematic evaluation of hairpin-containing transcripts and human genetic variation. Genome Research 2017, 27: 374-384. PMID: 28087842, PMCID: PMC5340965, DOI: 10.1101/gr.208900.116.Peer-Reviewed Original ResearchConceptsPri-miRNA processingHuman genetic variationGenetic variationPrimary sequence motifsPrimary microRNA processingMiRNA biogenesisDisease-causing mutationsPri-miRNAsPrimary miRNAsSequence motifsMiRNA hairpinsMicroRNA processingMature microRNAsSequence featuresRNA hairpinsComputational pipelineNovel determinantStem lengthUnpaired basesHairpinTranscriptsStemBiogenesisGenomeMiRNAs
2016
Analysis of protein-coding genetic variation in 60,706 humans
Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O’Donnell-Luria A, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won HH, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, McCarroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG. Analysis of protein-coding genetic variation in 60,706 humans. Nature 2016, 536: 285-291. PMID: 27535533, PMCID: PMC5018207, DOI: 10.1038/nature19057.Peer-Reviewed Original ResearchConceptsGenetic variationProtein-coding genetic variationProtein-coding genesDNA sequence dataHuman genetic diversityHuman genetic variationDNA sequence changesHuman disease phenotypesCandidate disease-causing variantsClasses of mutationsExome Aggregation ConsortiumProtein-truncating variantsMutational recurrenceStrong selectionGenetic diversitySequence dataDiverse ancestryDisease-causing variantsSequence changesSequence variantsGenesDisease phenotypeFunctional interpretationVariantsDirect evidencePatterns of genic intolerance of rare copy number variation in 59,898 human exomes
Ruderfer DM, Hamamsy T, Lek M, Karczewski KJ, Kavanagh D, Samocha KE, Daly M, MacArthur D, Fromer M, Purcell S. Patterns of genic intolerance of rare copy number variation in 59,898 human exomes. Nature Genetics 2016, 48: 1107-1111. PMID: 27533299, PMCID: PMC5042837, DOI: 10.1038/ng.3638.Peer-Reviewed Original ResearchConceptsGenic copy number variantsHuman genetic variationExome Aggregation ConsortiumRare copy number variationsCopy number variationsCopy number variantsExome sequencing dataGenetic variationGenic intoleranceHuman exomeSequencing dataPersonal genomesNumber variationsNumber variantsGenomeIntegrated databaseExomeVariationVariantsConsortium
2015
Genetic diversity of disease-associated loci in Turkish population
Karaca S, Cesuroglu T, Karaca M, Erge S, Polimanti R. Genetic diversity of disease-associated loci in Turkish population. Journal Of Human Genetics 2015, 60: 193-198. PMID: 25716910, DOI: 10.1038/jhg.2015.8.Peer-Reviewed Original ResearchConceptsHealth-related traitsGenetic diversityNon-European ancestryHuman genetic variationDisease-associated lociGenetic structureComplex traitsGenetic variationTraitsEuropean individualsGenesEast populationDiversityGenetic featuresAncestryPolygenic scoresMiddle East populationLociPopulationPeculiar genetic featuresGenetic predispositionHuman groupsLarge numberTurkish populationLast findingHuman Genome Diversity Project: History
Radin J. Human Genome Diversity Project: History. 2015, 306-310. DOI: 10.1016/b978-0-08-097086-8.82037-1.Peer-Reviewed Original Research
2014
Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells
Lee MN, Ye C, Villani AC, Raj T, Li W, Eisenhaure TM, Imboywa SH, Chipendo PI, Ran FA, Slowikowski K, Ward LD, Raddassi K, McCabe C, Lee MH, Frohlich IY, Hafler DA, Kellis M, Raychaudhuri S, Zhang F, Stranger BE, Benoist CO, De Jager PL, Regev A, Hacohen N. Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells. Science 2014, 343: 1246980. PMID: 24604203, PMCID: PMC4124741, DOI: 10.1126/science.1246980.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutoimmune DiseasesCommunicable DiseasesDendritic CellsEscherichia coliFemaleGene-Environment InteractionGenetic LociGenome-Wide Association StudyHEK293 CellsHost-Pathogen InteractionsHumansInfluenza A virusInterferon Regulatory Factor-7Interferon-betaLipopolysaccharidesMaleMiddle AgedPolymorphism, Single NucleotideQuantitative Trait LociSTAT Transcription FactorsTranscriptomeYoung AdultConceptsGenetic variationPathogen-responsive genesHuman genetic variationGenetic variantsIRF transcription factorsCommon genetic variantsType I IFN inductionFunctional annotationExpression responsesTranscription factorsI IFN inductionCausal variantsPathogen sensingEnvironmental stimuliComplex diseasesCommon variantsCommon allelesIFN inductionComputational approachVariantsCellsInductionGenesInterindividual variationSTAT
2013
Functional diversity of the glutathione peroxidase gene family among human populations: implications for genetic predisposition to disease and drug response
Polimanti R, Fuciarelli M, Destro-Bisol G, Battaggia C. Functional diversity of the glutathione peroxidase gene family among human populations: implications for genetic predisposition to disease and drug response. Pharmacogenomics 2013, 14: 1037-1045. PMID: 23837478, DOI: 10.2217/pgs.13.99.Peer-Reviewed Original ResearchConceptsGlutathione peroxidase gene familyPeroxidase gene familyHuman genetic variationFunctional prediction analysisHigh functional impactHuman populationGenomes Project dataGene familyFunctional diversityRedox regulationGenetic variationDrug responseFunctional differencesFunctional impactAdaptation signalsCommon variantsDiverse responsesGlutathione peroxidaseRare variantsGPX3GPX1Prediction analysisVariantsDiverse susceptibilityDiversityA genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A
Lane J, McLaren P, Dorrell L, Shianna K, Stemke A, Pelak K, Moore S, Oldenburg J, Alvarez-Roman M, Angelillo-Scherrer A, Boehlen F, Bolton-Maggs P, Brand B, Brown D, Chiang E, Cid-Haro A, Clotet B, Collins P, Colombo S, Dalmau J, Fogarty P, Giangrande P, Gringeri A, Iyer R, Katsarou O, Kempton C, Kuriakose P, Lin J, Makris M, Manco-Johnson M, Tsakiris D, Martinez-Picado J, Mauser-Bunschoten E, Neff A, Oka S, Oyesiku L, Parra R, Peter-Salonen K, Powell J, Recht M, Shapiro A, Stine K, Talks K, Telenti A, Wilde J, Yee T, Wolinsky S, Martinson J, Hussain S, Bream J, Jacobson L, Carrington M, Goedert J, Haynes B, McMichael A, Goldstein D, Fellay J, Immunology F. A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A. Human Molecular Genetics 2013, 22: 1903-1910. PMID: 23372042, PMCID: PMC3613165, DOI: 10.1093/hmg/ddt033.Peer-Reviewed Original ResearchMeSH KeywordsAdultDisease ResistanceDNA Copy Number VariationsEpistasis, GeneticFactor VIIIFemaleGene DeletionGenetic Predisposition to DiseaseGenome-Wide Association StudyHemophilia AHeterozygoteHIV InfectionsHIV SeropositivityHomozygoteHumansLogistic ModelsMaleMeta-Analysis as TopicMiddle AgedPhenotypePolymorphism, Single NucleotideProspective StudiesReceptors, CCR5ConceptsGenome-wide association studiesCopy number variantsSingle nucleotide polymorphismsFactor VIII infusionsHemophilia treatment centersAssociation studiesHost resistance factorsGenetic variantsSingle nucleotide polymorphism imputationGenome-wide genetic variantsHemophilia AHIV-1Genome-wide significanceIntroduction of viral inactivation proceduresGenome-wide approachesHuman genetic variationSusceptibility to HIV-1 infectionResistance to HIV infectionHIV-uninfected casesPathway enrichment analysisHIV-1 infectionHIV-1 susceptibilityHIV-infected controlsHIV-infected individualsHIV-1 serostatus
2012
Human genetic variation of CYP450 superfamily: analysis of functional diversity in worldwide populations
Polimanti R, Piacentini S, Manfellotto D, Fuciarelli M. Human genetic variation of CYP450 superfamily: analysis of functional diversity in worldwide populations. Pharmacogenomics 2012, 13: 1951-1960. PMID: 23215887, DOI: 10.2217/pgs.12.163.Peer-Reviewed Original ResearchConceptsGenetic diversityHuman genetic diversityHuman genetic variationHuman Genome Diversity ProjectFunctional differencesHuman populationRole of CYP450Functional diversityGenetic variationRelated clinical phenotypesHigh differentiationCYP450 genesHapMap dataDiversity ProjectHuman adaptationF-statisticsDiversityGenesWorldwide populationDrug responseComputational analysisClinical phenotypeAdaptationCYP450Interethnic differences
2011
Genome–virome interactions: examining the role of common viral infections in complex disease
Foxman EF, Iwasaki A. Genome–virome interactions: examining the role of common viral infections in complex disease. Nature Reviews Microbiology 2011, 9: 254-264. PMID: 21407242, PMCID: PMC3678363, DOI: 10.1038/nrmicro2541.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHuman genetic variationLarge regulatory networkHost-virus interactionsCrohn's diseaseRegulatory networksHost genesGenetic variationModel hostGenomic technologiesAutophagy pathwayAntiviral defenseViral infectionAdditional host factorsEnvironmental conditionsComplex diseasesCommon viral infectionsCases of asthmaSubsequent disease developmentGenesHostHost factorsDisease developmentParticular virus
2010
Progress in Cytogenetics: Implications for Child Psychopathology
Hoffman EJ, State MW. Progress in Cytogenetics: Implications for Child Psychopathology. Journal Of The American Academy Of Child & Adolescent Psychiatry 2010, 49: 736-751. PMID: 20643309, DOI: 10.1016/j.jaac.2010.03.016.Peer-Reviewed Original ResearchConceptsChromosomal structureHuman genetic variationSequence of DNAChromosomal variationMicroarray-based detectionGenetic variationGenetic basisMolecular cytogeneticsGenetic underpinningsMicroarray technologySynapse functionKey discoveriesStructural variationsRecent findingsUnaffected individualsChromosomal studiesCytogenetic investigationsDevelopmental neuropsychiatric disordersCytogeneticsLight microscopyChromosomesGeneticsDNADramatic increasePhenotype
2007
Human genetic variation of medical significance
Kidd K, Kidd J. Human genetic variation of medical significance. 2007, 51-62. DOI: 10.1093/acprof:oso/9780199207466.003.0005.Peer-Reviewed Original ResearchGenetic variationNormal genetic variationRandom genetic driftSignificant genetic variationLoss of variationHuman genetic variationAllele frequency variationHuman evolutionary historyEvolutionary historyGenetic driftNatural selectionModern humansMedical significanceGeographic regionsLociHumansVariationSelectionDemographyMetabolismTaste perceptionComplex waysIsolationMigration
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