2025
Psychiatric genetics in the diverse landscape of Latin American populations
Bruxel E, Rovaris D, Belangero S, Chavarría-Soley G, Cuellar-Barboza A, Martínez-Magaña J, Nagamatsu S, Nievergelt C, Núñez-Ríos D, Ota V, Peterson R, Sloofman L, Adams A, Albino E, Alvarado A, Andrade-Brito D, Arguello-Pascualli P, Bandeira C, Bau C, Bulik C, Buxbaum J, Cappi C, Corral-Frias N, Corrales A, Corsi-Zuelli F, Crowley J, Cupertino R, da Silva B, De Almeida S, De la Hoz J, Forero D, Fries G, Gelernter J, González-Giraldo Y, Grevet E, Grice D, Hernández-Garayua A, Hettema J, Ibáñez A, Ionita-Laza I, Lattig M, Lima Y, Lin Y, López-León S, Loureiro C, Martínez-Cerdeño V, Martínez-Levy G, Melin K, Moreno-De-Luca D, Muniz Carvalho C, Olivares A, Oliveira V, Ormond R, Palmer A, Panzenhagen A, Passos-Bueno M, Peng Q, Pérez-Palma E, Prieto M, Roussos P, Sanchez-Roige S, Santamaría-García H, Shansis F, Sharp R, Storch E, Tavares M, Tietz G, Torres-Hernández B, Tovo-Rodrigues L, Trelles P, Trujillo-ChiVacuan E, Velásquez M, Vera-Urbina F, Voloudakis G, Wegman-Ostrosky T, Zhen-Duan J, Zhou H, Santoro M, Nicolini H, Atkinson E, Giusti-Rodríguez P, Montalvo-Ortiz J. Psychiatric genetics in the diverse landscape of Latin American populations. Nature Genetics 2025, 57: 1074-1088. PMID: 40175716, PMCID: PMC12133068, DOI: 10.1038/s41588-025-02127-z.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesPsychiatric genomicsPsychiatric genome-wide association studiesLarge-scale genome-wide association studiesGenetic risk lociNon-European populationsGenetic diversityRisk lociGenetic admixtureBurden of psychiatric disordersAssociation studiesPsychiatric disordersEuropean ancestryPsychiatric geneticsGenomeHealthcare disparitiesConsortium effortLatin American populationsPromote equityEnvironmental factorsDiversityAmerican populationDiverse landscapeLociAncestryRisk factors affecting polygenic score performance across diverse cohorts
Hui D, Dudek S, Kiryluk K, Walunas T, Kullo I, Wei W, Tiwari H, Peterson J, Chung W, Davis B, Khan A, Kottyan L, Limdi N, Feng Q, Puckelwartz M, Weng C, Smith J, Karlson E, Center R, BioBank P, Jarvik G, Ritchie M. Risk factors affecting polygenic score performance across diverse cohorts. ELife 2025, 12: rp88149. PMID: 39851248, PMCID: PMC11771958, DOI: 10.7554/elife.88149.Peer-Reviewed Original ResearchConceptsBody mass indexPolygenic scoresAssociated with body mass indexPolygenic score performancePhysical activityStandard deviation changeAlcohol consumptionMass indexDiverse cohortInteraction effectsRisk factorsBlood lipidsDeviation changeQuintileScore performanceCohortCovariatesBinary covariateAncestryModel R<sup>2</sup>Continuous covariatesDifferencesRisk factors affecting polygenic score performance across diverse cohorts
Hui D, Dudek S, Kiryluk K, Walunas T, Kullo I, Wei W, Tiwari H, Peterson J, Chung W, Davis B, Khan A, Kottyan L, Limdi N, Feng Q, Puckelwartz M, Weng C, Smith J, Karlson E, Jarvik G, Ritchie M. Risk factors affecting polygenic score performance across diverse cohorts. ELife 2025, 12 DOI: 10.7554/elife.88149.3.Peer-Reviewed Original ResearchBody mass indexPolygenic scoresAssociated with body mass indexPolygenic score performancePhysical activityStandard deviation changeBMI effectsBMI individualsAlcohol consumptionDiverse cohortMass indexInteraction effectsRisk factorsBlood lipidsDeviation changeQuintileScore performanceCohortCovariatesBinary covariateAncestryContinuous covariatesModel R 2DifferencesScoresTrans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies
Consortium M, Adams M, Streit F, Meng X, Awasthi S, Adey B, Choi K, Chundru V, Coleman J, Ferwerda B, Foo J, Gerring Z, Giannakopoulou O, Gupta P, Hall A, Harder A, Howard D, Hübel C, Kwong A, Levey D, Mitchell B, Ni G, Ota V, Pain O, Pathak G, Schulte E, Shen X, Thorp J, Walker A, Yao S, Zeng J, Zvrskovec J, Aarsland D, Actkins K, Adli M, Agerbo E, Aichholzer M, Aiello A, Air T, Als T, Andersson E, Andlauer T, Arolt V, Ask H, Bäckman J, Badola S, Ballard C, Banasik K, Bass N, Beekman A, Belangero S, Bigdeli T, Binder E, Bjerkeset O, Bjornsdottir G, Børte S, Bränn E, Braun A, Brodersen T, Brückl T, Brunak S, Bruun M, Burmeister M, Buspavanich P, Bybjerg-Grauholm J, Byrne E, Cai J, Campbell A, Campbell M, Campos A, Castelao E, Cervilla J, Chaumette B, Chen C, Chen H, Chen Z, Cichon S, Colodro-Conde L, Corbett A, Corfield E, Couvy-Duchesne B, Craddock N, Dannlowski U, Davies G, de Geus E, Deary I, Degenhardt F, Dehghan A, DePaulo J, Deuschle M, Didriksen M, Dinh K, Direk N, Djurovic S, Docherty A, Domschke K, Dowsett J, Drange O, Dunn E, Eaton W, Einarsson G, Eley T, Elsheikh S, Engelmann J, Benros M, Erikstrup C, Escott-Price V, Fabbri C, Fang Y, Finer S, Frank J, Free R, Gallo L, Gao H, Gill M, Gilles M, Goes F, Gordon S, Grove J, Gudbjartsson D, Gutierrez B, Hahn T, Hall L, Hansen T, Haraldsson M, Hartman C, Havdahl A, Hayward C, Heilmann-Heimbach S, Herms S, Hickie I, Hjalgrim H, Hjerling-Leffler J, Hoffmann P, Homuth G, Horn C, Hottenga J, Hougaard D, Hovatta I, Huang Q, Hucks D, Huider F, Hunt K, Ialongo N, Ising M, Isometsä E, Jansen R, Jiang Y, Jones I, Jones L, Jonsson L, Kanai M, Karlsson R, Kasper S, Kendler K, Kessler R, Kloiber S, Knowles J, Koen N, Kraft J, Kranzler H, Krebs K, Kallak T, Kutalik Z, Lahtela E, Lake M, Larsen M, Lenze E, Lewins M, Lewis G, Li L, Lin B, Lin K, Lind P, Liu Y, MacIntyre D, MacKinnon D, Maher B, Maier W, Marshe V, Martinez-Levy G, Matsuda K, Mbarek H, McGuffin P, Medland S, Meinert S, Mikkelsen C, Mikkelsen S, Milaneschi Y, Millwood I, Molina E, Mondimore F, Mortensen P, Mulsant B, Naamanka J, Najman J, Nauck M, Nenadić I, Nielsen K, Nolt I, Nordentoft M, Nöthen M, Nyegaard M, O'Donovan M, Oddsson A, Oliveira A, Olsen C, Oskarsson H, Ostrowski S, Owen M, Packer R, Palviainen T, Pan P, Pato C, Pato M, Pedersen N, Pedersen O, Peyrot W, Potash J, Preisig M, Preuss M, Quiroz J, Renteria M, Reynolds C, Rice J, Sakaue S, Santoro M, Schoevers R, Schork A, Schulze T, Send T, Shi J, Sigurdsson E, Singh K, Sinnamon G, Sirignano L, Smeland O, Smith D, Sofer T, Sørensen E, Srinivasan S, Stefansson H, Stefansson K, Straub P, Su M, Tadic A, Teismann H, Teumer A, Thapar A, Thomson P, Thørner L, Topaloudi A, Tsai S, Tzoulaki I, Uhl G, Uitterlinden A, Ullum H, Umbricht D, Ursano R, Van der Auwera S, van Hemert A, Veluchamy A, Viktorin A, Völzke H, Walters G, Wang X, Wani A, Weissman M, Wellmann J, Whiteman D, Wildman D, Willemsen G, Williams A, Winsvold B, Witt S, Xiong Y, Zillich L, Zwart J, Team T, Group C, Team E, Team G, Psychiatry H, Project T, Program V, Andreassen O, Baune B, Berger K, Boomsma D, Børglum A, Breen G, Cai N, Coon H, Copeland W, Creese B, Cruz-Fuentes C, Czamara D, Davis L, Derks E, Domenici E, Elliott P, Forstner A, Gawlik M, Gelernter J, Grabe H, Hamilton S, Hveem K, John C, Kaprio J, Kircher T, Krebs M, Kuo P, Landén M, Lehto K, Levinson D, Li Q, Lieb K, Loos R, Lu Y, Lucae S, Luykx J, Maes H, Magnusson P, Martin H, Martin N, McQuillin A, Middeldorp C, Milani L, Mors O, Müller D, Müller-Myhsok B, Okada Y, Oldehinkel A, Paciga S, Palmer C, Paschou P, Penninx B, Perlis R, Peterson R, Pistis G, Polimanti R, Porteous D, Posthuma D, Rabinowitz J, Reichborn-Kjennerud T, Reif A, Rice F, Ricken R, Rietschel M, Rivera M, Rück C, Salum G, Schaefer C, Sen S, Serretti A, Skalkidou A, Smoller J, Stein D, Stein F, Stein M, Sullivan P, Tesli M, Thorgeirsson T, Tiemeier H, Timpson N, Uddin M, Uher R, van Heel D, Verweij K, Walters R, Wassertheil-Smoller S, Wendland J, Werge T, Zwinderman A, Kuchenbaecker K, Wray N, Ripke S, Lewis C, McIntosh A. Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies. Cell 2025, 188: 640-652.e9. PMID: 39814019, PMCID: PMC11829167, DOI: 10.1016/j.cell.2024.12.002.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesCell-type enrichment analysisSingle-cell dataTrans-ancestryAdmixed ancestrySingle-cell analysisFine-mappingPotential repurposing opportunitiesAssociation studiesGene associationsEnrichment analysisReceptor clusteringPolygenic scoresRepurposing opportunitiesPostsynaptic densityCell typesStudies of depressionMedium spiny neuronsAncestryAntidepressant targetSpiny neuronsAmygdala neuronsLociBiological targetsEffective treatmentGenetics of Depression
Levey D, Gelernter J. Genetics of Depression. 2025, 363-374. DOI: 10.1093/med/9780197640654.003.0028.Peer-Reviewed Original ResearchGenome-wide association studiesMajor depressive disorderWell-powered genome-wide association studiesStudy of Major Depressive DisorderAbstract Major depressive disorderAssociation studiesTrait heterogeneityGWAS studiesGenetic relationshipsRisk gene variantsEpidemiological studiesGene variantsDepressive disorderModerate heritabilityFollow-upClinical implicationsPotential clinical implicationsTraitsPopulation diversityRiskEquitable benefitsBiobankStatus of studiesHistorical familyAncestry
2024
Evaluation of imputation performance of multiple reference panels in a Pakistani population
Xu J, Liu D, Hassan A, Genovese G, Cote A, Fennessy B, Cheng E, Charney A, Knowles J, Ayub M, Peterson R, Bigdeli T, Huckins L. Evaluation of imputation performance of multiple reference panels in a Pakistani population. Human Genetics And Genomics Advances 2024, 6: 100395. PMID: 39696820, PMCID: PMC11759560, DOI: 10.1016/j.xhgg.2024.100395.Peer-Reviewed Original ResearchGenome-wide association studiesReference panelImputation accuracyMultiple reference panelsPakistani individualsGenotype imputationAssociation studiesGenotype dataAncestry compositionEuropean individualsSample sizeTOPMedDiverse populationsPakistani populationImputationGenomeAncestryIndividualsGenotypesPopulationVariantsFuture panelsGenome-wide meta-analysis of myasthenia gravis uncovers new loci and provides insights into polygenic prediction
Braun A, Shekhar S, Levey D, Straub P, Kraft J, Panagiotaropoulou G, Heilbron K, Awasthi S, Meleka Hanna R, Hoffmann S, Stein M, Lehnerer S, Mergenthaler P, Elnahas A, Topaloudi A, Koromina M, Palviainen T, Asbjornsdottir B, Stefansson H, Skuladóttir A, Jónsdóttir I, Stefansson K, Reis K, Esko T, Palotie A, Leypoldt F, Stein M, Fontanillas P, Kaprio J, Gelernter J, Davis L, Paschou P, Tannemaat M, Verschuuren J, Kuhlenbäumer G, Gregersen P, Huijbers M, Stascheit F, Meisel A, Ripke S. Genome-wide meta-analysis of myasthenia gravis uncovers new loci and provides insights into polygenic prediction. Nature Communications 2024, 15: 9839. PMID: 39537604, PMCID: PMC11560923, DOI: 10.1038/s41467-024-53595-6.Peer-Reviewed Original ResearchConceptsPerformance of polygenic risk scoresGenome-wide significant hitsGenome-wide association studiesGenome-wide meta-analysisControls of European ancestryGenetic architecturePolygenic risk scoresSignificant hitsAssociation studiesPhenotypic variationPolygenic predictionEuropean ancestryAssociated with early-onsetHuman leukocyte antigen allelesLociEarly-onsetReplication studyNeuromuscular junctionMyasthenia gravisAutoantibody-mediated diseasesAntigen allelesAllelesAncestryDisease manifestationsLate-onset MGF95. LOCAL ANCESTRY-AWARE META-ANALYSIS OF GENOME-WIDE ASSOCIATION STUDIES FOR ALCOHOL CONSUMPTION IN LATIN AMERICAN POPULATIONS
Martinez-Magana J, Atkinson E, Giusti-Rodriguez P, Santoro M, Wassertheil-Smoller S, Daviglus M, Perreira K, Nicolini H, Pereira A, Belangero S, Moyses-Oliveira M, Tucker K, Ordovas J, Villatoro-Velazquez J, Montalvo-Ortiz J. F95. LOCAL ANCESTRY-AWARE META-ANALYSIS OF GENOME-WIDE ASSOCIATION STUDIES FOR ALCOHOL CONSUMPTION IN LATIN AMERICAN POPULATIONS. European Neuropsychopharmacology 2024, 87: 256. DOI: 10.1016/j.euroneuro.2024.08.506.Peer-Reviewed Original ResearchGenome-wide association studiesGenome-wide association study studiesAncestry-specific effectsIntergenic variantAlcohol consumptionAncestry-specific lociNative-American ancestryFrequency of alcohol consumptionAssociated with alcohol consumptionMeta-analysisLocal ancestryAdmixed populationsGWA studiesGenomic backgroundAssociation studiesSLIT3 geneMAGI1 genesGenomics ConsortiumGenetic associationGenesLatin American populationsAfrican ancestryGenetic liabilityUnited StatesAncestrySemi-supervised machine learning method for predicting homogeneous ancestry groups to assess Hardy-Weinberg equilibrium in diverse whole-genome sequencing studies
Shyr D, Dey R, Li X, Zhou H, Boerwinkle E, Buyske S, Daly M, Gibbs R, Hall I, Matise T, Reeves C, Stitziel N, Zody M, Neale B, Lin X. Semi-supervised machine learning method for predicting homogeneous ancestry groups to assess Hardy-Weinberg equilibrium in diverse whole-genome sequencing studies. American Journal Of Human Genetics 2024, 111: 2129-2138. PMID: 39270648, PMCID: PMC11480788, DOI: 10.1016/j.ajhg.2024.08.018.Peer-Reviewed Original ResearchHardy-Weinberg equilibriumWhole-genome sequencing studiesWhole-genome sequencingHomogeneous ancestryWGS studiesDownstream analysisAssociation analysisPresence of population structureAncestry groupsGenetic ancestry groupsPopulation structureSequencing studiesSelf-reported raceGenetic researchQuality variantsAncestrySubsets of samplesProgram centersVariantsIncreasing diversityHeterogeneous sampleAncestralAssociationGeneticsSequenceCopy-number variants differ in frequency across genetic ancestry groups
Schultz L, Knighton A, Huguet G, Saci Z, Jean-Louis M, Mollon J, Knowles E, Glahn D, Jacquemont S, Almasy L. Copy-number variants differ in frequency across genetic ancestry groups. Human Genetics And Genomics Advances 2024, 5: 100340. PMID: 39138864, PMCID: PMC11401192, DOI: 10.1016/j.xhgg.2024.100340.Peer-Reviewed Original ResearchCopy number variantsAncestry groupsDeleterious copy number variantsRecurrent copy number variantsNon-European ancestry groupsUK BiobankGenetic ancestry groupsGenetic ancestryEuropean ancestry groupsReplication cohortFamily cohortProbe associationsAncestryCopyVariantsHealth outcomesCognitive phenotypesCommunity populationAutism spectrum disorderPhenotypeCohortFolate metabolism and risk of childhood acute lymphoblastic leukemia: a genetic pathway analysis from the Childhood Cancer and Leukemia International Consortium
Metayer C, Spector L, Scheurer M, Jeon S, Scott R, Takagi M, Clavel J, Manabe A, Ma X, Hailu E, Lupo P, Urayama K, Bonaventure A, Kato M, Meirhaeghe A, Chiang C, Morimoto L, Wiemels J. Folate metabolism and risk of childhood acute lymphoblastic leukemia: a genetic pathway analysis from the Childhood Cancer and Leukemia International Consortium. Cancer Epidemiology Biomarkers & Prevention 2024, 33: 1248-1252. PMID: 38904462, PMCID: PMC11369612, DOI: 10.1158/1055-9965.epi-24-0189.Peer-Reviewed Original ResearchSingle nucleotide polymorphismsGenome-wide dataAncestry groupsFolate metabolic pathwayGenetic variantsChildhood cancerMetabolic pathwaysGenetic pathway analysisRisk of childhood ALLRisk of childhood acute lymphoblastic leukemiaGene-folate interactionsChildhood ALL riskCase-control studyDNA methylationMETAL softwareGenetic studiesNucleotide polymorphismsPathway analysisMeta-analysis of original dataALL riskGenetic effectsAncestryFolate pathwayMaternal genetic effectsFolate intakeCharacterizing genetic profiles for high triglyceride levels in U.S. patients of African ancestry
Jiang L, Gangireddy S, Dickson A, Xin Y, Yan C, Kawai V, Cox N, Linton M, Wei W, Stein C, Feng Q. Characterizing genetic profiles for high triglyceride levels in U.S. patients of African ancestry. Journal Of Lipid Research 2024, 65: 100569. PMID: 38795861, PMCID: PMC11231545, DOI: 10.1016/j.jlr.2024.100569.Peer-Reviewed Original ResearchIndividuals of AAElectronic health recordsMild-to-moderate HTGGenetic risk factorsAfrican ancestryEuropean ancestryGenetic profileIndividuals of European ancestryRisk factorsNormal TGLongitudinal electronic health recordsSevere hypertriglyceridemiaPolygenic risk scoresCohort of AA patientsPatients of African ancestryAPOA5 p.Metabolic genesFunctional variantsCardiovascular risk factorsHigher triglyceride levelsHealth recordsVariant allelesAncestryRisk scoreAA patientsExploring the relationship between admixture and genetic susceptibility to attention deficit hyperactivity disorder in two Latin American cohorts
Garzón Rodríguez N, Briceño-Balcázar I, Nicolini H, Martínez-Magaña J, Genis-Mendoza A, Flores-Lázaro J, Villatoro Velázquez J, Bustos Gamiño M, Medina-Mora M, Quiroz-Padilla M. Exploring the relationship between admixture and genetic susceptibility to attention deficit hyperactivity disorder in two Latin American cohorts. Journal Of Human Genetics 2024, 69: 373-380. PMID: 38714835, PMCID: PMC11269173, DOI: 10.1038/s10038-024-01246-5.Peer-Reviewed Original ResearchGenome-wide association analysisSingle-nucleotide polymorphismsSingle-nucleotide variantsSingle-nucleotideRisk-associated lociGenome-wide significanceRisk single-nucleotide polymorphismsAttention deficit hyperactivity disorderLocal ancestryAssociation lociIntergenic regionAdmixture proportionsAncestral componentsGenomic ancestryAssociation analysisAncestry levelsEuropean ancestryGenetic associationEuropean componentDeficit hyperactivity disorderAncestryGenomeGenesGenetic susceptibilityHyperactivity disorderCirculating Proteins and IgA Nephropathy
Tang C, Chen P, Xu L, Lv J, Shi S, Zhou X, Liu L, Zhang H. Circulating Proteins and IgA Nephropathy. Journal Of The American Society Of Nephrology 2024, 35: 1045-1057. PMID: 38687828, PMCID: PMC11377805, DOI: 10.1681/asn.0000000000000379.Peer-Reviewed Original ResearchProtein-protein interaction networkProtein-disease pairsColocalization analysisInteraction networkEast Asian ancestryMendelian randomizationPotential drug targetsDrug repurposing opportunitiesVariant annotationAncestry populationsIdentified proteinsNetwork Mendelian randomizationMendelian randomization studiesAsian ancestryDrug targetsProteinAncestryEast AsiansTherapeutic targetColocalizationCirculating proteinsCausal effectsMedicationTargetAnnotationGenetic drivers of heterogeneity in type 2 diabetes pathophysiology
Suzuki K, Hatzikotoulas K, Southam L, Taylor H, Yin X, Lorenz K, Mandla R, Huerta-Chagoya A, Melloni G, Kanoni S, Rayner N, Bocher O, Arruda A, Sonehara K, Namba S, Lee S, Preuss M, Petty L, Schroeder P, Vanderwerff B, Kals M, Bragg F, Lin K, Guo X, Zhang W, Yao J, Kim Y, Graff M, Takeuchi F, Nano J, Lamri A, Nakatochi M, Moon S, Scott R, Cook J, Lee J, Pan I, Taliun D, Parra E, Chai J, Bielak L, Tabara Y, Hai Y, Thorleifsson G, Grarup N, Sofer T, Wuttke M, Sarnowski C, Gieger C, Nousome D, Trompet S, Kwak S, Long J, Sun M, Tong L, Chen W, Nongmaithem S, Noordam R, Lim V, Tam C, Joo Y, Chen C, Raffield L, Prins B, Nicolas A, Yanek L, Chen G, Brody J, Kabagambe E, An P, Xiang A, Choi H, Cade B, Tan J, Broadaway K, Williamson A, Kamali Z, Cui J, Thangam M, Adair L, Adeyemo A, Aguilar-Salinas C, Ahluwalia T, Anand S, Bertoni A, Bork-Jensen J, Brandslund I, Buchanan T, Burant C, Butterworth A, Canouil M, Chan J, Chang L, Chee M, Chen J, Chen S, Chen Y, Chen Z, Chuang L, Cushman M, Danesh J, Das S, de Silva H, Dedoussis G, Dimitrov L, Doumatey A, Du S, Duan Q, Eckardt K, Emery L, Evans D, Evans M, Fischer K, Floyd J, Ford I, Franco O, Frayling T, Freedman B, Genter P, Gerstein H, Giedraitis V, González-Villalpando C, González-Villalpando M, Gordon-Larsen P, Gross M, Guare L, Hackinger S, Hakaste L, Han S, Hattersley A, Herder C, Horikoshi M, Howard A, Hsueh W, Huang M, Huang W, Hung Y, Hwang M, Hwu C, Ichihara S, Ikram M, Ingelsson M, Islam M, Isono M, Jang H, Jasmine F, Jiang G, Jonas J, Jørgensen T, Kamanu F, Kandeel F, Kasturiratne A, Katsuya T, Kaur V, Kawaguchi T, Keaton J, Kho A, Khor C, Kibriya M, Kim D, Kronenberg F, Kuusisto J, Läll K, Lange L, Lee K, Lee M, Lee N, Leong A, Li L, Li Y, Li-Gao R, Ligthart S, Lindgren C, Linneberg A, Liu C, Liu J, Locke A, Louie T, Luan J, Luk A, Luo X, Lv J, Lynch J, Lyssenko V, Maeda S, Mamakou V, Mansuri S, Matsuda K, Meitinger T, Melander O, Metspalu A, Mo H, Morris A, Moura F, Nadler J, Nalls M, Nayak U, Ntalla I, Okada Y, Orozco L, Patel S, Patil S, Pei P, Pereira M, Peters A, Pirie F, Polikowsky H, Porneala B, Prasad G, Rasmussen-Torvik L, Reiner A, Roden M, Rohde R, Roll K, Sabanayagam C, Sandow K, Sankareswaran A, Sattar N, Schönherr S, Shahriar M, Shen B, Shi J, Shin D, Shojima N, Smith J, So W, Stančáková A, Steinthorsdottir V, Stilp A, Strauch K, Taylor K, Thorand B, Thorsteinsdottir U, Tomlinson B, Tran T, Tsai F, Tuomilehto J, Tusie-Luna T, Udler M, Valladares-Salgado A, van Dam R, van Klinken J, Varma R, Wacher-Rodarte N, Wheeler E, Wickremasinghe A, van Dijk K, Witte D, Yajnik C, Yamamoto K, Yamamoto K, Yoon K, Yu C, Yuan J, Yusuf S, Zawistowski M, Zhang L, Zheng W, Raffel L, Igase M, Ipp E, Redline S, Cho Y, Lind L, Province M, Fornage M, Hanis C, Ingelsson E, Zonderman A, Psaty B, Wang Y, Rotimi C, Becker D, Matsuda F, Liu Y, Yokota M, Kardia S, Peyser P, Pankow J, Engert J, Bonnefond A, Froguel P, Wilson J, Sheu W, Wu J, Hayes M, Ma R, Wong T, Mook-Kanamori D, Tuomi T, Chandak G, Collins F, Bharadwaj D, Paré G, Sale M, Ahsan H, Motala A, Shu X, Park K, Jukema J, Cruz M, Chen Y, Rich S, McKean-Cowdin R, Grallert H, Cheng C, Ghanbari M, Tai E, Dupuis J, Kato N, Laakso M, Köttgen A, Koh W, Bowden D, Palmer C, Kooner J, Kooperberg C, Liu S, North K, Saleheen D, Hansen T, Pedersen O, Wareham N, Lee J, Kim B, Millwood I, Walters R, Stefansson K, Ahlqvist E, Goodarzi M, Mohlke K, Langenberg C, Haiman C, Loos R, Florez J, Rader D, Ritchie M, Zöllner S, Mägi R, Marston N, Ruff C, van Heel D, Finer S, Denny J, Yamauchi T, Kadowaki T, Chambers J, Ng M, Sim X, Below J, Tsao P, Chang K, McCarthy M, Meigs J, Mahajan A, Spracklen C, Mercader J, Boehnke M, Rotter J, Vujkovic M, Voight B, Morris A, Zeggini E. Genetic drivers of heterogeneity in type 2 diabetes pathophysiology. Nature 2024, 627: 347-357. PMID: 38374256, PMCID: PMC10937372, DOI: 10.1038/s41586-024-07019-6.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesChromatinCoronary Artery DiseaseDiabetes Mellitus, Type 2Diabetic NephropathiesDisease ProgressionEndothelial CellsEnteroendocrine CellsEpigenomicsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIslets of LangerhansMultifactorial InheritancePeripheral Arterial DiseaseSingle-Cell AnalysisConceptsGenome-wide association study dataIndividuals of diverse ancestryRegions of open chromatinAncestry groupsGenome-wide significanceSingle-cell epigenomicsCases of T2DT2D signalsAssociation signalsObesity-related processesOpen chromatinDiverse ancestryTrait associationsDrivers of heterogeneityGenetic driversProgression of T2DEnteroendocrine cellsType 2 diabetes pathophysiologyGenetic contributionMolecular mechanismsPolygenic scoresAncestryLociPancreatic isletsStudy data
2023
Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications
Levey D, Galimberti M, Deak J, Wendt F, Bhattacharya A, Koller D, Harrington K, Quaden R, Johnson E, Gupta P, Biradar M, Lam M, Cooke M, Rajagopal V, Empke S, Zhou H, Nunez Y, Kranzler H, Edenberg H, Agrawal A, Smoller J, Lencz T, Hougaard D, Børglum A, Demontis D, Gaziano J, Gandal M, Polimanti R, Stein M, Gelernter J. Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications. Nature Genetics 2023, 55: 2094-2103. PMID: 37985822, PMCID: PMC10703690, DOI: 10.1038/s41588-023-01563-z.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphism-based heritabilityMulti-ancestry genome-wide association studyAssociation studiesMillion Veteran ProgramGenome-wide association studiesWide significant lociWide association studySignificant lociReference panelSmall populationDisease biologyAncestryAmerican ancestryHeritabilityVeteran ProgramNumerous medical comorbiditiesLung cancer riskRelationship analysisLociBiologyPublic health implicationsEast AsiansPublic health consequencesMedical comorbiditiesCigarette smokingGenome-wide association studies and cross-population meta-analyses investigating short and long sleep duration
Austin-Zimmerman I, Levey D, Giannakopoulou O, Deak J, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Concato J, Buysse D, Gaziano J, Gottlieb D, Polimanti R, Stein M, Bramon E, Gelernter J. Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration. Nature Communications 2023, 14: 6059. PMID: 37770476, PMCID: PMC10539313, DOI: 10.1038/s41467-023-41249-y.Peer-Reviewed Original ResearchConceptsAssociation studiesGenome-wide association studiesGenetic correlationsWide association studyLinkage disequilibrium scorePositive genetic correlationSleep traitsIndependent lociMillion Veteran ProgramTraitsAncestryUK BiobankVeteran ProgramMendelian randomisationLociHeritabilitySNPsPhenotypeEast AsiansSimilar patternCardiometabolic phenotypesGenetic Variation and Sensory Perception of a Pediatric Formulation of Ibuprofen: Can a Medicine Taste Too Good for Some?
Mennella J, Kan M, Lowenthal E, Saraiva L, Mainland J, Himes B, Pepino M. Genetic Variation and Sensory Perception of a Pediatric Formulation of Ibuprofen: Can a Medicine Taste Too Good for Some? International Journal Of Molecular Sciences 2023, 24: 13050. PMID: 37685855, PMCID: PMC10487938, DOI: 10.3390/ijms241713050.Peer-Reviewed Original ResearchConceptsGenetic ancestryEuropean genetic ancestryTaste receptor genesIndependent of ancestryAfrican genetic ancestryGenetic variationFormulations of ibuprofenEpigenetic factorsAncestryReceptor geneDouble-blind cohort studyUrge to coughPerception of palatabilityRisk of accidental ingestionPersonality variationCohort studyPediatric formulationsSensory phenotypesThroat sensationChemesthetic sensationsMedicinal tasteTingling sensationPanelistsAdult panelistsDiverse populationsLATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry.
Katsumata Y, Fardo D, Shade L, Bowen J, Crane P, Jarvik G, Keene C, Larson E, McCormick W, McCurry S, Mukherjee S, Kowall N, McKee A, Honig R, Lawrence S, Vonsattel J, Williamson J, Small S, Burke J, Hulette C, Welsh-Bohmer K, Gearing M, Lah J, Levey A, Wingo T, Apostolova L, Farlow M, Ghetti B, Saykin A, Spina S, Albert M, Lyketsos C, Troncoso J, Frosch M, Green R, Growdon J, Hyman B, Tanzi R, Potter H, Dickson D, Ertekin-Taner N, Graff-Radford N, Parisi J, Petersen R, Duara R, Buxbaum J, Goate A, Sano M, Masurkar A, Wisniewski T, Bigio E, Mesulam M, Weintraub S, Vassar R, Kaye J, Quinn J, Woltjer R, Barnes L, Bennett D, Schneider J, Yu L, Henderson V, Fallon K, Harrell L, Marson D, Roberson E, DeCarli C, Jin L, Olichney J, Kim R, LaFerla F, Monuki E, Head E, Sultzer D, Geschwind D, Vinters H, Chesselet M, Galasko D, Brewer J, Boxer A, Karydas A, Kramer J, Miller B, Rosen H, Seeley W, Burns J, Swerdlow R, Abner E, Fardo D, Van Eldik L, Albin R, Lieberman A, Paulson H, Arnold S, Trojanowski J, Van Deerlin V, Hamilton R, Kamboh M, Lopez O, Becker J, Cao C, Raj A, Smith A, Chui H, Miller C, Ringman J, Schneider L, Bird T, Sonnen J, Yu C, Grabowski T, Peskind E, Raskind M, Li G, Tsuang D, Asthana S, Atwood C, Carlsson C, Sager M, Chin N, Craft S, Cairns N, Morris J, Cruchaga C, Strittmatter S, Reiman E, Beach T, Huentelman M, Hardy J, Myers A, Kauwe J, Hakonarson H, Blacker D, Montine T, Baldwin C, Farrer L, Jun G, Lunetta K, Bush W, Haines J, Lerner A, Zhou X, Barral S, Reitz C, Vardarajan B, Mayeux R, Beecham G, Carney R, Cuccaro M, Gilbert J, Hamilton-Nelson K, Kunkle B, Martin E, Pericak-Vance M, Vance J, Cantwell L, Kuzma A, Malamon J, Naj A, Qu L, Schellenberg G, Valladares O, Wang L, Zhao Y, Leverenz J, De Jager P, Evans D, Katz M, Lipton R, Boeve B, Allen M, Carrasquillo M, Younkin S, Kukull W, Faber K, Foroud T, Pavlik V, Massman P, Darby E, Rodriguear M, Khaleeq A, Royall D, Stevens A, Ory M, DeToledo J, Wilms H, Johnson K, Perez V, Hernandez M, Wilhelmsen K, Tilson J, Chasse S, Barber R, Fairchild T, O’Bryant S, Knebl J, Hall J, Johnson L, Mains D, Alvarez L, Gamboa A, Paydarfar D, Bertelson J, Woon M, Ayres G, Aguirre A, Palmer R, Polk M, Adams P, Huebinger R, Reisch J, Rosenberg R, Cullum M, Williams B, Quiceno M, Hynan L, Smith J, Davis B, Nguyen T, Rogaeva E, George-Hyslop P, Nelson P. LATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry. Journal Of Neuropathology & Experimental Neurology 2023, 82: 760-768. PMID: 37528055, PMCID: PMC10440720, DOI: 10.1093/jnen/nlad059.Peer-Reviewed Original ResearchConceptsSingle nucleotide variantsLimbic-predominant age-related TDP-43 encephalopathyAfrican ancestryRisk allelesIndividuals of African ancestryRisk-associated allelesTDP-43 proteinopathyGenetic risk factorsNucleotide variantsAllele frequenciesGenetic determinantsGenomics ConsortiumPersons of African ancestryTDP-43AllelesAncestryNational Alzheimer's Coordinating CenterDisease pathologyGenetic factorsNeuropathological featuresGRNAfrican American subjectsHippocampal sclerosisABCC9HS pathologyEfficient reconstruction of cell lineage trees for cell ancestry and cancer
Jang Y, Fasching L, Bae T, Tomasini L, Schreiner J, Szekely A, Fernandez T, Leckman J, Vaccarino F, Abyzov A. Efficient reconstruction of cell lineage trees for cell ancestry and cancer. Nucleic Acids Research 2023, 51: e57-e57. PMID: 37026484, PMCID: PMC10250207, DOI: 10.1093/nar/gkad254.Peer-Reviewed Original ResearchConceptsLineage treesCell ancestryCell lineage treesFirst cell divisionStem cell linesPluripotent stem cell lineLineage reconstructionInduced pluripotent stem cell lineCell divisionCancer progressionLineage representationCell linesMosaic mutationsHuman skin fibroblastsTreesMutationsAncestrySkin fibroblastsMultiple cellsGenomeLineagesZygotesLinesFibroblastsCells
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