2022
Discovery of 42 genome-wide significant loci associated with dyslexia
Doust C, Fontanillas P, Eising E, Gordon SD, Wang Z, Alagöz G, Molz B, Pourcain B, Francks C, Marioni R, Zhao J, Paracchini S, Talcott J, Monaco A, Stein J, Gruen J, Olson R, Willcutt E, DeFries J, Pennington B, Smith S, Wright M, Martin N, Auton A, Bates T, Fisher S, Luciano M. Discovery of 42 genome-wide significant loci associated with dyslexia. Nature Genetics 2022, 54: 1621-1629. PMID: 36266505, PMCID: PMC9649434, DOI: 10.1038/s41588-022-01192-y.Peer-Reviewed Original ResearchConceptsGenome-wide significant lociSignificant lociIndependent genome-wide significant lociWide association studyGenetic covarianceAssociation studiesGenetic markersLociGenetic etiologyEuropean ancestryTraitsPolygenic scoresCrucial life skillGenesHeritabilityIndependent cohortAncestryFamily studiesDiscoveryOrthographic Depth May Influence the Degree of Severity of Maze Learning Performance in Children at Risk for Reading Disorder
Gabel L, Battison A, Truong D, Lindström E, Voss K, Yu Y, Roongruengratanakul S, Shyntassov K, Riebesell S, Toumanios N, Nielsen-Pheiffer C, Paniagua S, Gruen J. Orthographic Depth May Influence the Degree of Severity of Maze Learning Performance in Children at Risk for Reading Disorder. Developmental Neuroscience 2022, 44: 651-670. PMID: 36223729, PMCID: PMC9928771, DOI: 10.1159/000527480.Peer-Reviewed Original ResearchConceptsLow reading skillsOrthographic depthReading skillsNative EnglishSame neural networkLack of textCognitive predictorsReading networkCognitive processesImpaired performanceGenetic riskLanguage orthographyDegree of impairmentDiverse sampleActivation patternsNeural networkNative GermansTaskOral reportingMazeOrthographyRecent researchImpairmentChildrenEnglish
2017
Enrichment of putatively damaging rare variants in the DYX2 locus and the reading-related genes CCDC136 and FLNC
Adams AK, Smith SD, Truong DT, Willcutt EG, Olson RK, DeFries JC, Pennington BF, Gruen JR. Enrichment of putatively damaging rare variants in the DYX2 locus and the reading-related genes CCDC136 and FLNC. Human Genetics 2017, 136: 1395-1405. PMID: 28866788, PMCID: PMC5702371, DOI: 10.1007/s00439-017-1838-z.Peer-Reviewed Original Research
2016
Multipoint genome-wide linkage scan for nonword repetition in a multigenerational family further supports chromosome 13q as a locus for verbal trait disorders
Truong DT, Shriberg LD, Smith SD, Chapman KL, Scheer-Cohen AR, DeMille MM, Adams AK, Nato AQ, Wijsman EM, Eicher JD, Gruen JR. Multipoint genome-wide linkage scan for nonword repetition in a multigenerational family further supports chromosome 13q as a locus for verbal trait disorders. Human Genetics 2016, 135: 1329-1341. PMID: 27535846, PMCID: PMC5065602, DOI: 10.1007/s00439-016-1717-z.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overChildChild, PreschoolChromosome MappingChromosomes, Human, Pair 13Drosophila ProteinsDyslexiaFemaleGenetic LinkageGenetic Predisposition to DiseaseGenotypeHumansLanguage DisordersLod ScoreMaleMembrane ProteinsMiddle AgedNuclear ProteinsPedigreeQuantitative Trait LociReadingSpeech DisordersWritingConceptsNonword repetitionSpecific language impairmentCognitive processesLanguage impairmentAuditory processingVerbal developmentMotor planningPerson's abilityRobust endophenotypesMultigenerational familiesLanguage traitsRepetitionDisordersGenome-wide linkage scanSpellingVariance component linkage analysisCausal genetic factorsMultipoint variance component linkage analysisMemoryEndophenotypesSpeechChromosome 13qFuture studiesPresent studyDeficitsExecutive Functions Contribute Uniquely to Reading Competence in Minority Youth
Jacobson LA, Koriakin T, Lipkin P, Boada R, Frijters JC, Lovett MW, Hill D, Willcutt E, Gottwald S, Wolf M, Bosson-Heenan J, Gruen JR, Mahone EM. Executive Functions Contribute Uniquely to Reading Competence in Minority Youth. Journal Of Learning Disabilities 2016, 50: 422-433. PMID: 26755569, PMCID: PMC5960349, DOI: 10.1177/0022219415618501.Peer-Reviewed Original ResearchConceptsExecutive functionAttentional switchingMinority youthDomain-general processesComponents of readingInformation processing speedHierarchical linear regressionWord readingExecutive skillsAssessment of individualsCompetent readingReading interventionLanguage skillsContextual wordsProcessing speedFluencyUnique contributionComprehensionSkillsYouthMinority backgroundsReadingEthnic minority groupsCaucasian samplesCompetence
2013
Genome‐wide association study of shared components of reading disability and language impairment
Eicher JD, Powers NR, Miller LL, Akshoomoff N, Amaral DG, Bloss CS, Libiger O, Schork NJ, Darst BF, Casey BJ, Chang L, Ernst T, Frazier J, Kaufmann WE, Keating B, Kenet T, Kennedy D, Mostofsky S, Murray SS, Sowell ER, Bartsch H, Kuperman JM, Brown TT, Hagler DJ, Dale AM, Jernigan TL, St. Pourcain B, Smith G, Ring SM, Gruen JR, for the Pediatric Imaging N. Genome‐wide association study of shared components of reading disability and language impairment. Genes Brain & Behavior 2013, 12: 792-801. PMID: 24024963, PMCID: PMC3904347, DOI: 10.1111/gbb.12085.Peer-Reviewed Original ResearchImaging-genetics in dyslexia: Connecting risk genetic variants to brain neuroimaging and ultimately to reading impairments
Eicher JD, Gruen JR. Imaging-genetics in dyslexia: Connecting risk genetic variants to brain neuroimaging and ultimately to reading impairments. Molecular Genetics And Metabolism 2013, 110: 201-212. PMID: 23916419, PMCID: PMC3800223, DOI: 10.1016/j.ymgme.2013.07.001.Peer-Reviewed Original ResearchAlleles of a Polymorphic ETV6 Binding Site in DCDC2 Confer Risk of Reading and Language Impairment
Powers NR, Eicher JD, Butter F, Kong Y, Miller LL, Ring SM, Mann M, Gruen JR. Alleles of a Polymorphic ETV6 Binding Site in DCDC2 Confer Risk of Reading and Language Impairment. American Journal Of Human Genetics 2013, 93: 19-28. PMID: 23746548, PMCID: PMC3710765, DOI: 10.1016/j.ajhg.2013.05.008.Peer-Reviewed Original ResearchMeSH KeywordsAllelesBase SequenceBinding SitesCase-Control StudiesDyslexiaGenetic Association StudiesHaplotypesHeLa CellsHumansLanguage Development DisordersLanguage TestsLinkage DisequilibriumMicrosatellite RepeatsMicrotubule-Associated ProteinsMolecular Sequence DataPhylogenyPolymorphism, GeneticPromoter Regions, GeneticProtein BindingProto-Oncogene Proteins c-etsRepressor ProteinsRisk FactorsAssociations of Prenatal Nicotine Exposure and the Dopamine Related Genes ANKK1 and DRD2 to Verbal Language
Eicher JD, Powers NR, Cho K, Miller LL, Mueller KL, Ring SM, Tomblin JB, Gruen JR. Associations of Prenatal Nicotine Exposure and the Dopamine Related Genes ANKK1 and DRD2 to Verbal Language. PLOS ONE 2013, 8: e63762. PMID: 23691092, PMCID: PMC3655151, DOI: 10.1371/journal.pone.0063762.Peer-Reviewed Original ResearchConceptsPrenatal nicotine exposureANKK1/DRD2Nicotine exposureNicotine dependenceDose-response fashionAvon Longitudinal StudyCase-control cohortAssociation of markersPrenatal environmental factorsPrenatal nicotineLanguage impairmentLanguage tasksNeurobehavioral disordersEtiological determinantsNeural circuitsUtero developmentLongitudinal studyDRD2Communication disordersRiskRelated pathwaysAssociationExposureDisordersANKK1
2012
Prenatal Exposure to Nicotine and Impaired Reading Performance
Cho K, Frijters JC, Zhang H, Miller LL, Gruen JR. Prenatal Exposure to Nicotine and Impaired Reading Performance. The Journal Of Pediatrics 2012, 162: 713-718.e2. PMID: 23122624, PMCID: PMC3577994, DOI: 10.1016/j.jpeds.2012.09.041.Peer-Reviewed Original ResearchConceptsSchool-aged childrenPrenatal nicotine exposureSkill outcomesAge childrenLongitudinal studyPotential mediatorsNicotine exposureSkills of childrenPhonological deficitPrenatal exposureRisk of underperformanceReading performanceSingle wordsAvon Longitudinal StudyLongitudinal samplePoor performanceLarge associationsNegative associationChildrenAreas of speedParentsSpellingFluencyNicotineComprehensionVariants in the DYX2 locus are associated with altered brain activation in reading-related brain regions in subjects with reading disability
Cope N, Eicher JD, Meng H, Gibson CJ, Hager K, Lacadie C, Fulbright RK, Constable RT, Page GP, Gruen JR. Variants in the DYX2 locus are associated with altered brain activation in reading-related brain regions in subjects with reading disability. NeuroImage 2012, 63: 148-156. PMID: 22750057, PMCID: PMC3518451, DOI: 10.1016/j.neuroimage.2012.06.037.Peer-Reviewed Original ResearchDCDC2 genetic variants and susceptibility to developmental dyslexia
Marino C, Meng H, Mascheretti S, Rusconi M, Cope N, Giorda R, Molteni M, Gruen JR. DCDC2 genetic variants and susceptibility to developmental dyslexia. Psychiatric Genetics 2012, 22: 25-30. PMID: 21881542, PMCID: PMC3232293, DOI: 10.1097/ypg.0b013e32834acdb2.Peer-Reviewed Original ResearchConceptsDevelopmental dyslexiaQuantitative transmission disequilibrium test analysesNonword readingNonword spellingOrthographic choiceMarker-trait associationsQuantitative trait lociDyslexiaMemory impairmentRelated readingsTrait lociQuantitative traitsQuantitative transmission disequilibrium testTransmission disequilibrium test analysisPhenotypic complexityAssociation evidenceGenetic linkageMemoryAssociation analysisDCDC2WordsGenetic variantsTransmission disequilibrium testReadingPerformance tests
2010
A Dyslexia-Associated Variant in DCDC2 Changes Gene Expression
Meng H, Powers NR, Tang L, Cope NA, Zhang PX, Fuleihan R, Gibson C, Page GP, Gruen JR. A Dyslexia-Associated Variant in DCDC2 Changes Gene Expression. Behavior Genetics 2010, 41: 58-66. PMID: 21042874, PMCID: PMC3053575, DOI: 10.1007/s10519-010-9408-3.Peer-Reviewed Original Research
2007
Genetic approaches to complications of prematurity.
Meng H, Gruen JR. Genetic approaches to complications of prematurity. Frontiers In Bioscience-Landmark 2007, 12: 2344-51. PMID: 17127244, DOI: 10.2741/2236.Peer-Reviewed Original ResearchConceptsNeonatal morbidityLow birth weight babiesBirth weight babiesComplications of prematurityGestational age groupsVLBW babiesWeight babiesBronchopulmonary dysplasiaIntraventricular hemorrhageSpecific therapyTherapeutic advancesClinical trialsAnimal modelsAge groupsGenetic componentMorbidityDizygotic twinsSignificant genetic componentBabiesMortalityComplex genetic diseasesTimely implementationRecent studiesGenetic diseasesEnterocolitisGuideline for data analysis of genomewide association studies.
Zhang H, Liu L, Wang X, Gruen JR. Guideline for data analysis of genomewide association studies. Cancer Genomics & Proteomics 2007, 4: 27-34. PMID: 17726238.Peer-Reviewed Original Research
2005
DCDC2 is associated with reading disability and modulates neuronal development in the brain
Meng H, Smith SD, Hager K, Held M, Liu J, Olson RK, Pennington BF, DeFries JC, Gelernter J, O'Reilly-Pol T, Somlo S, Skudlarski P, Shaywitz SE, Shaywitz BA, Marchione K, Wang Y, Paramasivam M, LoTurco JJ, Page GP, Gruen JR. DCDC2 is associated with reading disability and modulates neuronal development in the brain. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 17053-17058. PMID: 16278297, PMCID: PMC1278934, DOI: 10.1073/pnas.0508591102.Peer-Reviewed Original Research
2001
Peaks of Linkage Are Localized by a BAC/PAC Contig of the 6p Reading Disability Locus
Ahn J, Won T, Zia A, Reutter H, Kaplan D, Sparks R, Gruen J. Peaks of Linkage Are Localized by a BAC/PAC Contig of the 6p Reading Disability Locus. Genomics 2001, 78: 19-29. PMID: 11707069, DOI: 10.1006/geno.2001.6645.Peer-Reviewed Original ResearchConceptsBacterial artificial chromosomeBAC/PAC contigHigh-resolution genetic studiesEntire chromosome 6Intermarker distanceArtificial chromosome contigPhysical mapping dataPeak of linkageSuccinic semialdehyde dehydrogenaseUncharacterized genesGenetic boundariesSequence tagsShort tandem repeatsArtificial chromosomesMarker orderClone contigNew contigPhysical mapGenetic lociLinkage peakCandidate genesPAC contigSemialdehyde dehydrogenaseContigsChromosome 6Human GABAB receptor 1 gene: Eight novel sequence variants
Hisama F, Gruen J, Choi J, Huseinovic M, Grigorenko E, Pauls D, Mattson R, Gelernter J, Wood F, Goei V. Human GABAB receptor 1 gene: Eight novel sequence variants. Human Mutation 2001, 17: 349-350. PMID: 11295833, DOI: 10.1002/humu.34.Peer-Reviewed Original ResearchMeSH KeywordsChromosome MappingChromosomes, Human, Pair 6DNA Mutational AnalysisDNA PrimersExonsGene FrequencyGenetic Predisposition to DiseaseGenetic VariationHumansIntronsMental DisordersMutationMutation, MissensePolymorphism, GeneticPolymorphism, Restriction Fragment LengthPolymorphism, Single-Stranded ConformationalReceptors, GABA-BUnited StatesConceptsNeurobehavioral disordersPrincipal inhibitory neurotransmitterHuman leukocyte antigen (HLA) regionInhibitory neurotransmitterPharmacogenetic studiesGene mutationsAntigen regionIntron variantsMissense mutationsDistinct mutationsDisordersLinkage studiesReceptor mapsAmerican populationGABBR1MutationsSusceptibility regionsEpilepsyCandidate genesDNA variantsGABANeurotransmittersSchizophreniaBrain
1999
Cloning of a Novel MHC-Encoded Serine Peptidase Highly Expressed by Cortical Epithelial Cells of the Thymus
Bowlus C, Ahn J, Chu T, Gruen J. Cloning of a Novel MHC-Encoded Serine Peptidase Highly Expressed by Cortical Epithelial Cells of the Thymus. Cellular Immunology 1999, 196: 80-86. PMID: 10527559, DOI: 10.1006/cimm.1999.1543.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigen PresentationAntigens, Differentiation, B-LymphocyteBase SequenceCarboxypeptidasesConsensus SequenceCosmidsEpithelial CellsFluorescent Antibody Technique, IndirectGenesHistocompatibility Antigens Class IIHumansIn Situ HybridizationLysosomesMajor Histocompatibility ComplexMiceMice, Inbred C57BLMolecular Sequence DataSequence AlignmentSequence Homology, Amino AcidSerine EndopeptidasesThymus GlandConceptsCortical thymic epithelial cellsAntigen-presenting cellsThymic epithelial cellsEpithelial cellsMHC class II presentationClass II antigen processingMHC class II antigen processingClass II presentationCortical epithelial cellsMajor histocompatibility complex regionThymic capsuleThymic cortexAntigen presentationT cellsSerine proteasesStrong stainingNovel MHCAntigen processingInvariant chainCathepsin SProteolytic milieuThymusPresentationSitu hybridizationStainingThe genomic organization of the histone clusters on human 6p21.3
Ahn J, Gruen J. The genomic organization of the histone clusters on human 6p21.3. Mammalian Genome 1999, 10: 768-770. PMID: 10384058, DOI: 10.1007/s003359901089.Peer-Reviewed Original Research