2025
Characterizing pleiotropy among bipolar disorder, schizophrenia, and major depression: a genome-wide cross-disorder meta-analysis
Friligkou E, Pathak G, Tylee D, De Lillo A, Koller D, Cabrera-Mendoza B, Polimanti R. Characterizing pleiotropy among bipolar disorder, schizophrenia, and major depression: a genome-wide cross-disorder meta-analysis. Psychological Medicine 2025, 55: e145. PMID: 40357923, PMCID: PMC12094657, DOI: 10.1017/s0033291725001217.Peer-Reviewed Original ResearchMeSH KeywordsBipolar DisorderDepressive Disorder, MajorGenetic PleiotropyGenome-Wide Association StudyHumansSchizophreniaTranscriptomeConceptsBipolar disorderPleiotropic lociCross-disorder meta-analysisGenome-wide association datasetGenome-wide analysisGenome-wide significanceTissue enrichment analysisBrain transcriptomic dataBrain transcriptome profilesPsychiatric Genomics ConsortiumCadherin signalingGenome-wideGenetic architectureGene discoveryDiagnostic boundariesPleiotropic variantsFrontal cortexReceptor-mediated signalingTranscriptome dataSchizophreniaGenetic mechanismsGenomics ConsortiumTranscriptome profilingAssociation datasetEnrichment analysisAlcohol use disorder and body mass index show genetic pleiotropy and shared neural associations
Malone S, Davis C, Piserchia Z, Setzer M, Toikumo S, Zhou H, Winterlind E, Gelernter J, Justice A, Leggio L, Rentsch C, Kranzler H, Gray J. Alcohol use disorder and body mass index show genetic pleiotropy and shared neural associations. Nature Human Behaviour 2025, 9: 1056-1066. PMID: 40164914, DOI: 10.1038/s41562-025-02148-y.Peer-Reviewed Original ResearchConceptsAlcohol use disorderUse disorderBrain regionsGenotype-Tissue ExpressionSingle-nucleotide polymorphismsPolygenic overlapAssociated with alcohol use disorderCaudate nucleus volumeBody mass indexMultiple brain regionsConjunctional false discovery rateNeurobiological overlapExecutive functionNeurobiological mechanismsNeural associationsBrain phenotypesNucleus volumeFalse discovery rate methodFalse discovery rateGenetic architectureVariant effectsMass indexGenetic pleiotropyDiscovery rateTissue enrichmentEnhanced insights into the genetic architecture of 3D cranial vault shape using pleiotropy-informed GWAS
Goovaerts S, Naqvi S, Hoskens H, Herrick N, Yuan M, Shriver M, Shaffer J, Walsh S, Weinberg S, Wysocka J, Claes P. Enhanced insights into the genetic architecture of 3D cranial vault shape using pleiotropy-informed GWAS. Communications Biology 2025, 8: 439. PMID: 40087503, PMCID: PMC11909261, DOI: 10.1038/s42003-025-07875-6.Peer-Reviewed Original ResearchMeSH KeywordsGenetic PleiotropyGenome-Wide Association StudyHumansPolymorphism, Single NucleotideSkullConceptsCranial vault shapeVault shapeGenomic lociGenetic discovery effortsSNP discoveryCraniofacial developmentGenetic architectureGWAS dataGWAS studiesTranscription factorsGenetic studiesCranial vaultGenetic understandingShape variationSignaling pathwayBrain shapeExperimental biologyBrain shape variationCraniofacial complexFDR methodLociDiscovery effortsFacial shapeWealth of knowledgeGWASBrain-wide pleiotropy investigation of alcohol drinking and tobacco smoking behaviors
Deiana G, He J, Cabrera-Mendoza B, Ciccocioppo R, Napolioni V, Polimanti R. Brain-wide pleiotropy investigation of alcohol drinking and tobacco smoking behaviors. Translational Psychiatry 2025, 15: 61. PMID: 39979292, PMCID: PMC11842717, DOI: 10.1038/s41398-025-03288-5.Peer-Reviewed Original ResearchConceptsImaging-derived phenotypesBrain imaging-derived phenotypesAlcohol drinkingBrain structuresProcessing of social cuesCorrelates of smoking behaviorRelationship of brain structureSequencing Consortium of AlcoholGlobal genetic correlationsSmoking behaviorSuperior longitudinal fasciculusAssociated with smoking initiationTobacco smokeTobacco smoking behaviorLatent causal variable approachesNicotine useBrain regionsPremotor cortexSocial cuesWhite matter hyperintensitiesLongitudinal fasciculusChemosensory processingCortical thicknessMendelian randomizationPleiotropic mechanisms
2022
Whole exome sequencing in dense families suggests genetic pleiotropy amongst Mendelian and complex neuropsychiatric syndromes
Ganesh S, Vemula A, Bhattacharjee S, Mathew K, Ithal D, Navin K, Nadella R, Viswanath B, Sullivan P, Jain S, Purushottam M. Whole exome sequencing in dense families suggests genetic pleiotropy amongst Mendelian and complex neuropsychiatric syndromes. Scientific Reports 2022, 12: 21128. PMID: 36476812, PMCID: PMC9729597, DOI: 10.1038/s41598-022-25664-7.Peer-Reviewed Original ResearchConceptsSequence kernel association testKernel association testWhole-exome sequencing studiesExome sequencing studiesUnique genesGenetic architectureCase-control association analysisDeleterious variantsSequencing studiesWhole-exome sequencingMendelian syndromesAssociation analysisCriteria of rarityPleiotropic influenceGenesWES studyFunctional consequencesSignificant overrepresentationGenetic pleiotropyExome sequencingAffected individualsFamilyImportant insightsUnrelated controlsAssociation TestMendelian randomization for causal inference accounting for pleiotropy and sample structure using genome-wide summary statistics
Hu X, Zhao J, Lin Z, Wang Y, Peng H, Zhao H, Wan X, Yang C. Mendelian randomization for causal inference accounting for pleiotropy and sample structure using genome-wide summary statistics. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2106858119. PMID: 35787050, PMCID: PMC9282238, DOI: 10.1073/pnas.2106858119.Peer-Reviewed Original ResearchMeSH KeywordsCausalityGenetic PleiotropyGenome-Wide Association StudyMendelian Randomization AnalysisPhenotypeReproducibility of Results
2020
Polygenic risk for autism spectrum disorder associates with anger recognition in a neurodevelopment-focused phenome-wide scan of unaffected youths from a population-based cohort
Wendt FR, Carvalho CM, Pathak GA, Gelernter J, Polimanti R. Polygenic risk for autism spectrum disorder associates with anger recognition in a neurodevelopment-focused phenome-wide scan of unaffected youths from a population-based cohort. PLOS Genetics 2020, 16: e1009036. PMID: 32941431, PMCID: PMC7523983, DOI: 10.1371/journal.pgen.1009036.Peer-Reviewed Original ResearchGenome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer
Lin Y, Nakatochi M, Hosono Y, Ito H, Kamatani Y, Inoko A, Sakamoto H, Kinoshita F, Kobayashi Y, Ishii H, Ozaka M, Sasaki T, Matsuyama M, Sasahira N, Morimoto M, Kobayashi S, Fukushima T, Ueno M, Ohkawa S, Egawa N, Kuruma S, Mori M, Nakao H, Adachi Y, Okuda M, Osaki T, Kamiya S, Wang C, Hara K, Shimizu Y, Miyamoto T, Hayashi Y, Ebi H, Kohmoto T, Imoto I, Kasugai Y, Murakami Y, Akiyama M, Ishigaki K, Matsuda K, Hirata M, Shimada K, Okusaka T, Kawaguchi T, Takahashi M, Watanabe Y, Kuriki K, Kadota A, Okada R, Mikami H, Takezaki T, Suzuki S, Yamaji T, Iwasaki M, Sawada N, Goto A, Kinoshita K, Fuse N, Katsuoka F, Shimizu A, Nishizuka SS, Tanno K, Suzuki K, Okada Y, Horikoshi M, Yamauchi T, Kadowaki T, Yu H, Zhong J, Amundadottir LT, Doki Y, Ishii H, Eguchi H, Bogumil D, Haiman CA, Le Marchand L, Mori M, Risch H, Setiawan VW, Tsugane S, Wakai K, Yoshida T, Matsuda F, Kubo M, Kikuchi S, Matsuo K. Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer. Nature Communications 2020, 11: 3175. PMID: 32581250, PMCID: PMC7314803, DOI: 10.1038/s41467-020-16711-w.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsGenome-wide significant lociLead single nucleotide polymorphismsGenome-wide association studiesGene variantsMeta-analysis identifiesEast Asian ancestryEast Asian originSignificant lociRisk lociFunctional analysisAssociation studiesPancreatic cancer susceptibilityRisk variantsNucleotide polymorphismsCell linesGene risk variantsCancer susceptibilityLociAsian ancestryKRAS activityAsian originVariantsPancreatic cancerPopulation
2019
Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders
Consortium C, Lee P, Anttila V, Won H, Feng Y, Rosenthal J, Zhu Z, Tucker-Drob E, Nivard M, Grotzinger A, Posthuma D, Wang M, Yu D, Stahl E, Walters R, Anney R, Duncan L, Ge T, Adolfsson R, Banaschewski T, Belangero S, Cook E, Coppola G, Derks E, Hoekstra P, Kaprio J, Keski-Rahkonen A, Kirov G, Kranzler H, Luykx J, Rohde L, Zai C, Agerbo E, Arranz M, Asherson P, Bækvad-Hansen M, Baldursson G, Bellgrove M, Belliveau R, Buitelaar J, Burton C, Bybjerg-Grauholm J, Casas M, Cerrato F, Chambert K, Churchhouse C, Cormand B, Crosbie J, Dalsgaard S, Demontis D, Doyle A, Dumont A, Elia J, Grove J, Gudmundsson O, Haavik J, Hakonarson H, Hansen C, Hartman C, Hawi Z, Hervás A, Hougaard D, Howrigan D, Huang H, Kuntsi J, Langley K, Lesch K, Leung P, Loo S, Martin J, Martin A, McGough J, Medland S, Moran J, Mors O, Mortensen P, Oades R, Palmer D, Pedersen C, Pedersen M, Peters T, Poterba T, Poulsen J, Ramos-Quiroga J, Reif A, Ribasés M, Rothenberger A, Rovira P, Sánchez-Mora C, Satterstrom F, Schachar R, Artigas M, Steinberg S, Stefansson H, Turley P, Walters G, Team 2, Werge T, Zayats T, Arking D, Bettella F, Buxbaum J, Christensen J, Collins R, Coon H, De Rubeis S, Delorme R, Grice D, Hansen T, Holmans P, Hope S, Hultman C, Klei L, Ladd-Acosta C, Magnusson P, Nærland T, Nyegaard M, Pinto D, Qvist P, Rehnström K, Reichenberg A, Reichert J, Roeder K, Rouleau G, Saemundsen E, Sanders S, Sandin S, St Pourcain B, Stefansson K, Sutcliffe J, Talkowski M, Weiss L, Willsey A, Agartz I, Akil H, Albani D, Alda M, Als T, Anjorin A, Backlund L, Bass N, Bauer M, Baune B, Bellivier F, Bergen S, Berrettini W, Biernacka J, Blackwood D, Bøen E, Budde M, Bunney W, Burmeister M, Byerley W, Byrne E, Cichon S, Clarke T, Coleman J, Craddock N, Curtis D, Czerski P, Dale A, Dalkner N, Dannlowski U, Degenhardt F, Di Florio A, Elvsåshagen T, Etain B, Fischer S, Forstner A, Forty L, Frank J, Frye M, Fullerton J, Gade K, Gaspar H, Gershon E, Gill M, Goes F, Gordon S, Gordon-Smith K, Green M, Greenwood T, Grigoroiu-Serbanescu M, Guzman-Parra J, Hauser J, Hautzinger M, Heilbronner U, Herms S, Hoffmann P, Holland D, Jamain S, Jones I, Jones L, Kandaswamy R, Kelsoe J, Kennedy J, Joachim O, Kittel-Schneider S, Kogevinas M, Koller A, Lavebratt C, Lewis C, Li Q, Lissowska J, Loohuis L, Lucae S, Maaser A, Malt U, Martin N, Martinsson L, McElroy S, McMahon F, McQuillin A, Melle I, Metspalu A, Millischer V, Mitchell P, Montgomery G, Morken G, Morris D, Müller-Myhsok B, Mullins N, Myers R, Nievergelt C, Nordentoft M, Adolfsson A, Nöthen M, Ophoff R, Owen M, Paciga S, Pato C, Pato M, Perlis R, Perry A, Potash J, Reinbold C, Rietschel M, Rivera M, Roberson M, Schalling M, Schofield P, Schulze T, Scott L, Serretti A, Sigurdsson E, Smeland O, Stordal E, Streit F, Strohmaier J, Thorgeirsson T, Treutlein J, Turecki G, Vaaler A, Vieta E, Vincent J, Wang Y, Witt S, Zandi P, Adan R, Alfredsson L, Ando T, Aschauer H, Baker J, Bencko V, Bergen A, Birgegård A, Perica V, Brandt H, Burghardt R, Carlberg L, Cassina M, Clementi M, Courtet P, Crawford S, Crow S, Crowley J, Danner U, Davis O, Degortes D, DeSocio J, Dick D, Dina C, Docampo E, Egberts K, Ehrlich S, Espeseth T, Fernández-Aranda F, Fichter M, Foretova L, Forzan M, Gambaro G, Giegling I, Gonidakis F, Gorwood P, Mayora M, Guo Y, Halmi K, Hatzikotoulas K, Hebebrand J, Helder S, Herpertz-Dahlmann B, Herzog W, Hinney A, Imgart H, Jiménez-Murcia S, Johnson C, Jordan J, Julià A, Kaminská D, Karhunen L, Karwautz A, Kas M, Kaye W, Kennedy M, Kim Y, Klareskog L, Klump K, Knudsen G, Landén M, Le Hellard S, Levitan R, Li D, Lichtenstein P, Maj M, Marsal S, McDevitt S, Mitchell J, Monteleone P, Monteleone A, Munn-Chernoff M, Nacmias B, Navratilova M, O’Toole J, Padyukov L, Pantel J, Papezova H, Rabionet R, Raevuori A, Ramoz N, Reichborn-Kjennerud T, Ricca V, Roberts M, Rujescu D, Rybakowski F, Scherag A, Schmidt U, Seitz J, Slachtova L, Landt M, Slopien A, Sorbi S, Southam L, Strober M, Tortorella A, Tozzi F, Treasure J, Tziouvas K, van Elburg A, Wade T, Wagner G, Walton E, Watson H, Wichmann H, Woodside D, Zeggini E, Zerwas S, Zipfel S, Adams M, Andlauer T, Berger K, Binder E, Boomsma D, Castelao E, Colodro-Conde L, Direk N, Docherty A, Domenici E, Domschke K, Dunn E, Foo J, de. Geus E, Grabe H, Hamilton S, Horn C, Hottenga J, Howard D, Ising M, Kloiber S, Levinson D, Lewis G, Magnusson P, Mbarek H, Middeldorp C, Mostafavi S, Nyholt D, Penninx B, Peterson R, Pistis G, Porteous D, Preisig M, Quiroz J, Schaefer C, Schulte E, Shi J, Smith D, Thomson P, Tiemeier H, Uher R, van der Auwera S, Weissman M, Alexander M, Begemann M, Bramon E, Buccola N, Cairns M, Campion D, Carr V, Cloninger C, Cohen D, Collier D, Corvin A, DeLisi L, Donohoe G, Dudbridge F, Duan J, Freedman R, Gejman P, Golimbet V, Godard S, Ehrenreich H, Hartmann A, Henskens F, Ikeda M, Iwata N, Jablensky A, Joa I, Jönsson E, Kelly B, Knight J, Konte B, Laurent-Levinson C, Lee J, Lencz T, Lerer B, Loughland C, Malhotra A, Mallet J, McDonald C, Mitjans M, Mowry B, Murphy K, Murray R, O’Neill F, Oh S, Palotie A, Pantelis C, Pulver A, Consortium P, Petryshen T, Quested D, Riley B, Sanders A, Schall U, Schwab S, Scott R, Sham P, Silverman J, Sim K, Steixner A, Tooney P, van Os J, Vawter P, Walsh D, Weiser M, Wildenauer D, Williams N, Wormley B, Consortium W, Zhang F, Androutsos C, Arnold P, Barr C, Barta C, Bey K, Bienvenu O, Black D, Brown L, Budman C, Cath D, Cheon K, Ciullo V, Coffey B, Cusi D, Davis L, Denys D, Depienne C, Dietrich A, Eapen V, Falkai P, Fernandez T, Garcia-Delgar B, Geller D, Gilbert D, Grados M, Greenberg E, Grünblatt E, Hagstrøm J, Hanna G, Hartmann A, Hedderly T, Heiman G, Heyman I, Hong H, Huang A, Huyser C, Ibanez-Gomez L, Khramtsova E, Kim Y, Kim Y, King R, Koh Y, Konstantinidis A, Kook S, Kuperman S, Leventhal B, Lochner C, Ludolph A, Madruga-Garrido M, Malaty I, Maras A, McCracken J, Meijer I, Mir P, Morer A, Müller-Vahl K, Münchau A, Murphy T, Naarden A, Nagy P, Nestadt G, Nestadt P, Nicolini H, Nurmi E, Okun M, Paschou P, Piras F, Piras F, Pittenger C, Plessen K, Richter M, Rizzo R, Robertson M, Roessner V, Ruhrmann S, Samuels J, Sandor P, Schlögelhofer M, Shin E, Singer H, Song D, Song J, Spalletta G, Stein D, Stewart S, Storch E, Stranger B, Stuhrmann M, Tarnok Z, Tischfield J, Tübing J, Visscher F, Vulink N, Wagner M, Walitza S, Wanderer S, Woods M, Worbe Y, Zai G, Zinner S, Sullivan P, Franke B, Daly M, Bulik C, McIntosh A, O’Donovan M, Zheutlin A, Andreassen O, Børglum A, Breen G, Edenberg H, Fanous A, Faraone S, Gelernter J, Mathews C, Mattheisen M, Mitchell K, Neale M, Nurnberger J, Ripke S, Santangelo S, Scharf J, Stein M, Thornton L, Walters J, Wray N, Geschwind D, Neale B, Kendler K, Smoller J. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders. Cell 2019, 179: 1469-1482.e11. PMID: 31835028, PMCID: PMC7077032, DOI: 10.1016/j.cell.2019.11.020.Peer-Reviewed Original ResearchMeSH KeywordsGenetic PleiotropyGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMental DisordersNeurogenesisQuantitative Trait LociPleiotropic requirements for human TDP-43 in the regulation of cell and organelle homeostasis
Roczniak-Ferguson A, Ferguson SM. Pleiotropic requirements for human TDP-43 in the regulation of cell and organelle homeostasis. Life Science Alliance 2019, 2: e201900358. PMID: 31527135, PMCID: PMC6749094, DOI: 10.26508/lsa.201900358.Peer-Reviewed Original ResearchConceptsMultiple amyotrophic lateral sclerosisTDP-43 target genesNormal TDP-43 functionSpecific target transcriptsCell biological consequencesRNA-binding proteinTDP-43Disease-causing mutantsRegulation of cellPleiotropic requirementMultiple neurodegenerative diseasesOrganelle homeostasisTarget transcriptsMRNA splicingKnockout cellsTranscriptomic analysisMultiple organellesTDP-43 functionTarget genesCytoplasmic aggregatesNuclear envelopeTDP-43 mutationsTDP-43 depletionHuman TDP-43Morphological defectsPenetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia in 106,160 Patients Across Four Health Care Systems
Zheutlin A, Dennis J, Karlsson Linnér R, Moscati A, Restrepo N, Straub P, Ruderfer D, Castro V, Chen C, Ge T, Huckins L, Charney A, Kirchner H, Stahl E, Chabris C, Davis L, Smoller J. Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia in 106,160 Patients Across Four Health Care Systems. American Journal Of Psychiatry 2019, 176: 846-855. PMID: 31416338, PMCID: PMC6961974, DOI: 10.1176/appi.ajp.2019.18091085.Peer-Reviewed Original ResearchConceptsPolygenic risk scoresHealth care systemCare systemGenetic riskAssociated with schizophreniaPolygenic risk score distributionPhenome-wide association studyMeasures of genetic riskRisk scoreHighest risk decileHealth care settingsElectronic health recordsOdds of schizophreniaAssociated with other phenotypesCare settingsRisk decileHealth recordsHigher oddsHealth consequencesResearch cohortAssociation studiesHealthEarly interventionMeta-analysisPersonality disorderProteostasis Environment Shapes Higher-Order Epistasis Operating on Antibiotic Resistance
Guerrero R, Scarpino S, Rodrigues J, Hartl D, Ogbunugafor C. Proteostasis Environment Shapes Higher-Order Epistasis Operating on Antibiotic Resistance. Genetics 2019, 212: 565-575. PMID: 31015194, PMCID: PMC6553834, DOI: 10.1534/genetics.119.302138.Peer-Reviewed Original ResearchConceptsHigher-order epistasisSNPs associated with resistancePatterns of epistasisControlled genetic backgroundSets of mutationsProteostasis environmentComplex traitsEpistatic interactionsBacterial enzymesEssential enzymeCell physiologyGenotypic contextEpistasisAntibiotic resistanceGenetic backgroundBackground sequencesAntimicrobial resistanceProteostasisBacterial resistanceGenetic modification technologyMutationsProteinEnzymeTraitsAntibiotics
2018
Genomewide Association Study of Alcohol Dependence and Related Traits in a Thai Population
Gelernter J, Zhou H, Nuñez YZ, Mutirangura A, Malison RT, Kalayasiri R. Genomewide Association Study of Alcohol Dependence and Related Traits in a Thai Population. Alcohol Clinical And Experimental Research 2018, 42: 861-868. PMID: 29460428, PMCID: PMC5916336, DOI: 10.1111/acer.13614.Peer-Reviewed Original ResearchConceptsGenomewide association studiesAssociation studiesRisk genesAldehyde dehydrogenase 2Prior biological informationAfrican ancestry populationsRelated traitsSame geneBiological informationAlcohol dehydrogenasesSignificant pleiotropyDehydrogenase BGenesFunctional variantsPsychiatric traitsGenomewide significant associationPleiotropy analysisTraitsAncestry populationsFirst genomewide association studyPleiotropyDehydrogenase 2Null variants
2017
Statistical Analysis of Multiple Phenotypes in Genetic Epidemiologic Studies: From Cross-Phenotype Associations to Pleiotropy
Salinas YD, Wang Z, DeWan AT. Statistical Analysis of Multiple Phenotypes in Genetic Epidemiologic Studies: From Cross-Phenotype Associations to Pleiotropy. American Journal Of Epidemiology 2017, 187: 855-863. PMID: 29020254, PMCID: PMC5889027, DOI: 10.1093/aje/kwx296.Peer-Reviewed Original Research
2016
Genetic factor common to schizophrenia and HIV infection is associated with risky sexual behavior: antagonistic vs. synergistic pleiotropic SNPs enriched for distinctly different biological functions
Wang Q, Polimanti R, Kranzler HR, Farrer LA, Zhao H, Gelernter J. Genetic factor common to schizophrenia and HIV infection is associated with risky sexual behavior: antagonistic vs. synergistic pleiotropic SNPs enriched for distinctly different biological functions. Human Genetics 2016, 136: 75-83. PMID: 27752767, PMCID: PMC5215962, DOI: 10.1007/s00439-016-1737-8.Peer-Reviewed Original ResearchA Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn’s Disease and Human Gut Microbiome Composition
Li D, Achkar JP, Haritunians T, Jacobs JP, Hui KY, D'Amato M, Brand S, Radford-Smith G, Halfvarson J, Niess JH, Kugathasan S, Büning C, Schumm LP, Klei L, Ananthakrishnan A, Aumais G, Baidoo L, Dubinsky M, Fiocchi C, Glas J, Milgrom R, Proctor DD, Regueiro M, Simms LA, Stempak JM, Targan SR, Törkvist L, Sharma Y, Devlin B, Borneman J, Hakonarson H, Xavier RJ, Daly M, Brant SR, Rioux JD, Silverberg MS, Cho JH, Braun J, McGovern DP, Duerr RH. A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn’s Disease and Human Gut Microbiome Composition. Gastroenterology 2016, 151: 724-732. PMID: 27492617, PMCID: PMC5037008, DOI: 10.1053/j.gastro.2016.06.051.Peer-Reviewed Original ResearchConceptsCrohn's diseaseMissense variantsMicrobiome compositionGut microbiome compositionInflammatory bowel disease lociCD risk allelesIBD controlsCD patientsUlcerative colitisBlood pressureIBD casesSolute carrier family 39Overweight individualsHealthy controlsLavage samplesLipid levelsFunctional genetic variantsCD casesIndependent cohortHuman gut microbiome compositionReplication cohortGut microbiomeAbstractTextRisk allelesDiseaseLoss of function mutations in ATP2A2 and psychoses: A case report and literature survey
Nakamura T, Kazuno A, Nakajima K, Kusumi I, Tsuboi T, Kato T. Loss of function mutations in ATP2A2 and psychoses: A case report and literature survey. Psychiatry And Clinical Neurosciences 2016, 70: 342-350. PMID: 27106560, DOI: 10.1111/pcn.12395.Peer-Reviewed Original ResearchMeSH KeywordsAdultBipolar DisorderDarier DiseaseFemaleGenetic PleiotropyHumansMutationSarcoplasmic Reticulum Calcium-Transporting ATPasesConceptsDarier's diseaseStop codonBipolar disorderGenome-wide association studiesEffects of loss-of-function mutationsMinigene splicing assayCase reports of patientsChromosome 12q23-24.1Mutations of ATP2A2Loss-of-function mutationsAutosomal dominant skin disorderAssociation of schizophreniaPathophysiology of psychosisPremature stop codonReports of patientsCausative genetic mutationsLGD mutationsComorbidity of psychosisATP2A2 mutationsSplice siteAssociation studiesSplicing assayCoding regionHeterozygous mutationsCase report
2015
Pleiotropic Analysis of Cancer Risk Loci on Esophageal Adenocarcinoma Risk
Lee E, Stram DO, Ek WE, Onstad LE, MacGregor S, Gharahkhani P, Ye W, Lagergren J, Shaheen NJ, Murray LJ, Hardie LJ, Gammon MD, Chow WH, Risch HA, Corley DA, Levine DM, Whiteman DC, Bernstein L, Bird NC, Vaughan TL, Wu AH. Pleiotropic Analysis of Cancer Risk Loci on Esophageal Adenocarcinoma Risk. Cancer Epidemiology Biomarkers & Prevention 2015, 24: 1801-1803. PMID: 26364162, PMCID: PMC4648999, DOI: 10.1158/1055-9965.epi-15-0596.Peer-Reviewed Original ResearchConceptsRisk of EACBody mass indexBarrett's esophagusEsophageal adenocarcinomaCommon cancerEffect modificationEsophageal adenocarcinoma riskMultiple cancer sitesRisk variantsGenome-wide association studiesGenetic susceptibility studiesCase patientsAdenocarcinoma riskMass indexCancer sitesGenetic risk variantsEsophagusPleiotropic genetic associationsControl participantsCancerHeartburnRiskMultiple testingGenetic associationCancer risk lociPervasive pleiotropy between psychiatric disorders and immune disorders revealed by integrative analysis of multiple GWAS
Wang Q, Yang C, Gelernter J, Zhao H. Pervasive pleiotropy between psychiatric disorders and immune disorders revealed by integrative analysis of multiple GWAS. Human Genetics 2015, 134: 1195-1209. PMID: 26340901, PMCID: PMC4630076, DOI: 10.1007/s00439-015-1596-8.Peer-Reviewed Original ResearchMeSH KeywordsArthritis, RheumatoidCentral Nervous SystemCrohn DiseaseGenetic PleiotropyGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansImmune System DiseasesMental DisordersNerve Tissue ProteinsOrgan SpecificityPolymorphism, Single NucleotideQuantitative Trait LociSchizophreniaSystems IntegrationConceptsImmune disordersPsychiatric disordersCrohn's diseaseDisorder pairsMHC regionPervasive pleiotropyIntegrative analysisGenome-wide association studiesImmune dysregulationImmunological mechanismsTreatment strategiesTraits/diseasesEpidemiological observationsPsychiatric diseasesBrain disordersSame effect directionDiseaseDisordersGenomic regionsRealm of psychiatryMost allelesStrong pleiotropyAnnotation resourcesChromosome 6Association studies
2014
GPA: A Statistical Approach to Prioritizing GWAS Results by Integrating Pleiotropy and Annotation
Chung D, Yang C, Li C, Gelernter J, Zhao H. GPA: A Statistical Approach to Prioritizing GWAS Results by Integrating Pleiotropy and Annotation. PLOS Genetics 2014, 10: e1004787. PMID: 25393678, PMCID: PMC4230845, DOI: 10.1371/journal.pgen.1004787.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesFunctional annotationGWAS datasetsAnnotation informationStatistical approachMultiple GWAS datasetsGenome-wide markersPowerful statistical methodsSingle-phenotype analysisCentral nervous system genesRisk variantsNervous system genesGenotype-Tissue Expression (GTEx) databaseComplex diseasesGWAS data setsSignificant pleiotropic effectsCommon risk basisDifferent complex diseasesDNase-seq dataCell linesStatistical inferenceGenetic architectureGWAS hitsGWAS resultsNovel statistical approach
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