Featured Publications
Genome-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 phenotypesMulti-ancestry study of the genetics of problematic alcohol use in over 1 million individuals
Zhou H, Kember R, Deak J, Xu H, Toikumo S, Yuan K, Lind P, Farajzadeh L, Wang L, Hatoum A, Johnson J, Lee H, Mallard T, Xu J, Johnston K, Johnson E, Nielsen T, Galimberti M, Dao C, Levey D, Overstreet C, Byrne E, Gillespie N, Gordon S, Hickie I, Whitfield J, Xu K, Zhao H, Huckins L, Davis L, Sanchez-Roige S, Madden P, Heath A, Medland S, Martin N, Ge T, Smoller J, Hougaard D, Børglum A, Demontis D, Krystal J, Gaziano J, Edenberg H, Agrawal A, Justice A, Stein M, Kranzler H, Gelernter J. Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals. Nature Medicine 2023, 29: 3184-3192. PMID: 38062264, PMCID: PMC10719093, DOI: 10.1038/s41591-023-02653-5.Peer-Reviewed Original ResearchGenome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci
Deak JD, Zhou H, Galimberti M, Levey DF, Wendt FR, Sanchez-Roige S, Hatoum AS, Johnson EC, Nunez YZ, Demontis D, Børglum AD, Rajagopal VM, Jennings MV, Kember RL, Justice AC, Edenberg HJ, Agrawal A, Polimanti R, Kranzler HR, Gelernter J. Genome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci. Molecular Psychiatry 2022, 27: 3970-3979. PMID: 35879402, PMCID: PMC9718667, DOI: 10.1038/s41380-022-01709-1.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significant risk lociAssociation studiesVariant associationsLarge-scale genome-wide association studiesGenetic correlationsSignificant risk lociPsychiatric Genomics ConsortiumMulti-trait analysisPolygenic risk score analysisSingle-variant associationsGWS lociGenetic architectureIndividuals of EuropeanGWS associationsRisk lociGene regionGenomics ConsortiumMillion Veteran ProgramSusceptibility lociAfrican ancestryLociRisk score analysisGenetic informativenessSNPs oneGenome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations
Kranzler HR, Zhou H, Kember RL, Vickers Smith R, Justice AC, Damrauer S, Tsao PS, Klarin D, Baras A, Reid J, Overton J, Rader DJ, Cheng Z, Tate JP, Becker WC, Concato J, Xu K, Polimanti R, Zhao H, Gelernter J. Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. Nature Communications 2019, 10: 1499. PMID: 30940813, PMCID: PMC6445072, DOI: 10.1038/s41467-019-09480-8.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesMillion Veteran Program sampleGenetic correlationsWide significant lociSignificant genetic correlationsPolygenic risk scoresCell type groupSignificant lociHeritable traitEnrichment analysisTraitsMultiple populationsLociPhenotypeProgram samples
2024
A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals
Jennings M, Martínez-Magaña J, Courchesne-Krak N, Cupertino R, Vilar-Ribó L, Bianchi S, Hatoum A, Atkinson E, Giusti-Rodriguez P, Montalvo-Ortiz J, Gelernter J, Artigas M, 23andMe I, Aslibekyan S, Auton A, Babalola E, Bell R, Bielenberg J, Bryc K, Bullis E, Coker D, Partida G, Dhamija D, Das S, Elson S, Eriksson N, Filshtein T, Fitch A, Fletez-Brant K, Fontanillas P, Freyman W, Granka J, Heilbron K, Hernandez A, Hicks B, Hinds D, Jewett E, Jiang Y, Kukar K, Kwong A, Lin K, Llamas B, Lowe M, McCreight J, McIntyre M, Micheletti S, Moreno M, Nandakumar P, Nguyen D, Noblin E, O'Connell J, Petrakovitz A, Poznik G, Reynoso A, Schumacher M, Shastri A, Shelton J, Shi J, Shringarpure S, Su Q, Tat S, Tchakouté C, Tran V, Tung J, Wang X, Wang W, Weldon C, Wilton P, Wong C, Elson S, Edenberg H, Fontanillas P, Palmer A, Sanchez-Roige S. A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals. EBioMedicine 2024, 103: 105086. PMID: 38580523, PMCID: PMC11121167, DOI: 10.1016/j.ebiom.2024.105086.Peer-Reviewed Original ResearchConceptsMultiple domains of healthDomains of healthEffects of alcohol consumptionAlcohol consumptionHealth outcomesPhenome-wide association studyAlcohol-related behaviorsCardio-metabolic healthPotential causal effectMendelian randomisation studiesGenome-wide association studiesPhenome-wide associationMR analysisPheWAS associationsMultiple domainsHypothesis-free approachPreventive medicineDiverse cohortPheWASAssociation studiesHealthReproductive healthAlcohol behaviorConsequences of drinkingEuropean cohort
2023
Genetic Underpinnings of the Transition From Alcohol Consumption to Alcohol Use Disorder: Shared and Unique Genetic Architectures in a Cross-Ancestry Sample
Kember R, Vickers-Smith R, Zhou H, Xu H, Jennings M, Dao C, Davis L, Sanchez-Roige S, Justice A, Gelernter J, Vujkovic M, Kranzler H. Genetic Underpinnings of the Transition From Alcohol Consumption to Alcohol Use Disorder: Shared and Unique Genetic Architectures in a Cross-Ancestry Sample. American Journal Of Psychiatry 2023, 180: 584-593. PMID: 37282553, PMCID: PMC10731616, DOI: 10.1176/appi.ajp.21090892.Peer-Reviewed Original ResearchIdentifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study
Xu H, Toikumo S, Crist R, Glogowska K, Jinwala Z, Deak J, Justice A, Gelernter J, Johnson E, Kranzler H, Kember R. Identifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study. Addiction 2023, 118: 1942-1952. PMID: 37156939, PMCID: PMC10754226, DOI: 10.1111/add.16229.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSignificant single nucleotide polymorphismsSubstance use traitsMulti-trait analysisAssociation studiesGenetic architectureUse traitsGenome-wide significant single nucleotide polymorphismsProtein-protein interaction analysisTrait genetic architectureNumber of lociPolygenic risk scoresEuropean ancestry individualsNovel lociSingle nucleotide polymorphismsGenetic lociGWAS studiesLociMultiple related phenotypesNucleotide polymorphismsRelated phenotypesTraitsNovel associationsMTAgBiobank samplesMulti-trait genome-wide association analyses leveraging alcohol use disorder findings identify novel loci for smoking behaviors in the Million Veteran Program
Cheng Y, Dao C, Zhou H, Li B, Kember R, Toikumo S, Zhao H, Gelernter J, Kranzler H, Justice A, Xu K. Multi-trait genome-wide association analyses leveraging alcohol use disorder findings identify novel loci for smoking behaviors in the Million Veteran Program. Translational Psychiatry 2023, 13: 148. PMID: 37147289, PMCID: PMC10162964, DOI: 10.1038/s41398-023-02409-2.Peer-Reviewed Original ResearchConceptsSingle-trait genome-wide association studiesGenome-wide association studiesNovel lociPower of GWASJoint genome-wide association studyGenome-wide significant lociMillion Veteran ProgramGenome-wide associationSubstance use traitsGWAS summary statisticsNovel genetic variantsMulti-trait analysisFunctional annotationUse traitsSignificant lociHeritable traitMultiple lociAssociation studiesColocalization analysisLociPleiotropic effectsMTAgVeteran ProgramGenetic variantsTraitsMulti‐omics cannot replace sample size in genome‐wide association studies
Baranger D, Hatoum A, Polimanti R, Gelernter J, Edenberg H, Bogdan R, Agrawal A. Multi‐omics cannot replace sample size in genome‐wide association studies. Genes Brain & Behavior 2023, 22: e12846. PMID: 36977197, PMCID: PMC10733567, DOI: 10.1111/gbb.12846.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesLarge genome-wide association studiesNovel genesMulti-omics dataMulti-omics informationAssociation studiesGenome-wide significant lociSmall genome-wide association studyBrain-related traitsGWAS sample sizesEarly genome-wide association studiesNovel gene discoveryGene discoverySignificant lociAdditional genesPositional mappingHeritable traitVariant discoverySimilar traitsGenesNovel variant discoveryTraitsDisease biologyLociDiscovery
2022
Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond
Gaddis N, Mathur R, Marks J, Zhou L, Quach B, Waldrop A, Levran O, Agrawal A, Randesi M, Adelson M, Jeffries PW, Martin NG, Degenhardt L, Montgomery GW, Wetherill L, Lai D, Bucholz K, Foroud T, Porjesz B, Runarsdottir V, Tyrfingsson T, Einarsson G, Gudbjartsson DF, Webb BT, Crist RC, Kranzler HR, Sherva R, Zhou H, Hulse G, Wildenauer D, Kelty E, Attia J, Holliday EG, McEvoy M, Scott RJ, Schwab SG, Maher BS, Gruza R, Kreek MJ, Nelson EC, Thorgeirsson T, Stefansson K, Berrettini WH, Gelernter J, Edenberg HJ, Bierut L, Hancock DB, Johnson EO. Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond. Scientific Reports 2022, 12: 16873. PMID: 36207451, PMCID: PMC9546890, DOI: 10.1038/s41598-022-21003-y.Peer-Reviewed Original ResearchConceptsGenome-wide significant associationMulti-trait genome-wide association studyNovel genome-wide significant associationsGenome-wide association studiesGenomic structural equationGene-based analysisRelated traitsAssociation studiesGenetic correlationsEuropean ancestryA118G variantConsortium dataNew geneticsG variantGWASPPP6CLociPleiotropicGeneticsVariantsTraitsPhenotypeOA phenotypeFurinAncestryPhenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample
Kember RL, Hartwell EE, Xu H, Rotenberg J, Almasy L, Zhou H, Gelernter J, Kranzler HR. Phenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample. Biological Psychiatry 2022, 93: 536-545. PMID: 36273948, PMCID: PMC9931661, DOI: 10.1016/j.biopsych.2022.08.010.Peer-Reviewed Original ResearchConceptsSubstance use disordersAlcohol use disorderOpioid use disorderPolygenic risk scoresUse disordersCo-occurring psychiatric disordersComprehensive psychiatric interviewSemi-Structured AssessmentElectronic health recordsControl subjectsLow prevalencePsychiatric interviewRisk scorePsychiatric disordersPhenome-wide association analysisDrug dependenceEuropean individualsHealth recordsLifetime cannabisPhenome-wide association studyDisordersAfrican ancestry individualsDSM diagnosesPopulation sampleGenetic liabilityIntegrating human brain proteomic data with genome-wide association study findings identifies novel brain proteins in substance use traits
Toikumo S, Xu H, Gelernter J, Kember RL, Kranzler HR. Integrating human brain proteomic data with genome-wide association study findings identifies novel brain proteins in substance use traits. Neuropsychopharmacology 2022, 47: 2292-2299. PMID: 35941285, PMCID: PMC9630289, DOI: 10.1038/s41386-022-01406-1.Peer-Reviewed Original ResearchConceptsSubstance use traitsProteome-wide association studyUse traitsProtein abundanceAssociation studiesBrain protein abundanceWide association studyGenome-wide association study summary statisticsHuman brain proteomeFine-mapping analysisGenetic risk lociBrain transcriptomic dataEuropean ancestry individualsOpioid use disorderProteomic abundanceTranscriptomic levelTranscriptomic dataAlcohol use disorderProteomic dataBrain proteomeGenetic lociTranscript levelsRisk lociGene expressionSignificant genesSex-Specific Genetic and Transcriptomic Liability to Neuroticism
Wendt FR, Pathak GA, Singh K, Stein MB, Koenen KC, Krystal JH, Gelernter J, Davis LK, Polimanti R. Sex-Specific Genetic and Transcriptomic Liability to Neuroticism. Biological Psychiatry 2022, 93: 243-252. PMID: 36244801, PMCID: PMC10508260, DOI: 10.1016/j.biopsych.2022.07.019.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesTranscriptomic profilesAssociation studiesSingle nucleotide polymorphism heritabilityGene expression variationGenome-wide significanceSex-specific geneticChromosomal variationTranscriptomic changesRisk lociExpression variationBiological processesMolecular pathwaysLociPolygenic associationSex-specific effectsGenetic correlatesPolygenic scoresUK BiobankGenetic riskNCOA6GeneticsHeritabilityPathwayFemalesAn Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes
Tylee DS, Lee YK, Wendt FR, Pathak GA, Levey DF, De Angelis F, Gelernter J, Polimanti R. An Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes. JAMA Psychiatry 2022, 79: 667-676. PMID: 35507366, PMCID: PMC9069342, DOI: 10.1001/jamapsychiatry.2022.0914.Peer-Reviewed Original ResearchConceptsRisk factorsImmune-related phenotypesMultivariable adjustmentUlcerative colitisCrohn's diseaseMendelian randomizationImmune-related disordersReciprocal risk factorsHealth-related behaviorsPsychiatric phenotypesFalse discovery rate correctionAllergic rhinitisGenetic association studiesGenetic associationInflammatory disordersClinical associationsMajor depressionImmune disordersMAIN OUTCOMEPsychiatric disordersSocial determinantsDisordersAssociation studiesColitisAsthmaGenetically regulated multi-omics study for symptom clusters of posttraumatic stress disorder highlights pleiotropy with hematologic and cardio-metabolic traits
Pathak GA, Singh K, Wendt FR, Fleming TW, Overstreet C, Koller D, Tylee DS, De Angelis F, Cabrera Mendoza B, Levey DF, Koenen KC, Krystal JH, Pietrzak RH, O’ Donell C, Gaziano JM, Falcone G, Stein MB, Gelernter J, Pasaniuc B, Mancuso N, Davis LK, Polimanti R. Genetically regulated multi-omics study for symptom clusters of posttraumatic stress disorder highlights pleiotropy with hematologic and cardio-metabolic traits. Molecular Psychiatry 2022, 27: 1394-1404. PMID: 35241783, PMCID: PMC9210390, DOI: 10.1038/s41380-022-01488-9.Peer-Reviewed Original ResearchConceptsLocal genetic correlationsCell type-specific expressionVanderbilt University biorepositoryMulti-omics studiesMulti-omics investigationsDorsolateral prefrontal cortex tissueGenomic evidenceLaboratory traitsSpecific expressionCardio-metabolic traitsMillion Veteran ProgramPrefrontal cortex tissueMiR-148GenesGenetic correlationsRegulatory profileTraitsProtein expressionCardiometabolic traitsExpressionVeteran ProgramCortex tissueBiological heterogeneitySplicingPrioritization approachUsing phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder
Wendt FR, Pathak GA, Deak JD, De Angelis F, Koller D, Cabrera-Mendoza B, Lebovitch DS, Levey DF, Stein MB, Kranzler HR, Koenen KC, Gelernter J, Huckins LM, Polimanti R. Using phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder. Molecular Psychiatry 2022, 27: 2206-2215. PMID: 35181757, PMCID: PMC9133008, DOI: 10.1038/s41380-022-01469-y.Peer-Reviewed Original Research
2021
Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information
Maihofer AX, Choi KW, Coleman JRI, Daskalakis NP, Denckla CA, Ketema E, Morey RA, Polimanti R, Ratanatharathorn A, Torres K, Wingo AP, Zai CC, Aiello AE, Almli LM, Amstadter AB, Andersen SB, Andreassen OA, Arbisi PA, Ashley-Koch AE, Austin SB, Avdibegović E, Borglum AD, Babić D, Bækvad-Hansen M, Baker DG, Beckham JC, Bierut LJ, Bisson JI, Boks MP, Bolger EA, Bradley B, Brashear M, Breen G, Bryant RA, Bustamante AC, Bybjerg-Grauholm J, Calabrese JR, Caldas-de-Almeida JM, Chen CY, Dale AM, Dalvie S, Deckert J, Delahanty DL, Dennis MF, Disner SG, Domschke K, Duncan LE, Džubur Kulenović A, Erbes CR, Evans A, Farrer LA, Feeny NC, Flory JD, Forbes D, Franz CE, Galea S, Garrett ME, Gautam A, Gelaye B, Gelernter J, Geuze E, Gillespie CF, Goçi A, Gordon SD, Guffanti G, Hammamieh R, Hauser MA, Heath AC, Hemmings SMJ, Hougaard DM, Jakovljević M, Jett M, Johnson EO, Jones I, Jovanovic T, Qin XJ, Karstoft KI, Kaufman ML, Kessler RC, Khan A, Kimbrel NA, King AP, Koen N, Kranzler HR, Kremen WS, Lawford BR, Lebois LAM, Lewis C, Liberzon I, Linnstaedt SD, Logue MW, Lori A, Lugonja B, Luykx JJ, Lyons MJ, Maples-Keller JL, Marmar C, Martin NG, Maurer D, Mavissakalian MR, McFarlane A, McGlinchey RE, McLaughlin KA, McLean SA, Mehta D, Mellor R, Michopoulos V, Milberg W, Miller MW, Morris CP, Mors O, Mortensen PB, Nelson EC, Nordentoft M, Norman SB, O'Donnell M, Orcutt HK, Panizzon MS, Peters ES, Peterson AL, Peverill M, Pietrzak RH, Polusny MA, Rice JP, Risbrough VB, Roberts AL, Rothbaum AO, Rothbaum BO, Roy-Byrne P, Ruggiero KJ, Rung A, Rutten BPF, Saccone NL, Sanchez SE, Schijven D, Seedat S, Seligowski AV, Seng JS, Sheerin CM, Silove D, Smith AK, Smoller JW, Sponheim SR, Stein DJ, Stevens JS, Teicher MH, Thompson WK, Trapido E, Uddin M, Ursano RJ, van den Heuvel LL, Van Hooff M, Vermetten E, Vinkers CH, Voisey J, Wang Y, Wang Z, Werge T, Williams MA, Williamson DE, Winternitz S, Wolf C, Wolf EJ, Yehuda R, Young KA, Young RM, Zhao H, Zoellner LA, Haas M, Lasseter H, Provost AC, Salem RM, Sebat J, Shaffer RA, Wu T, Ripke S, Daly MJ, Ressler KJ, Koenen KC, Stein MB, Nievergelt CM. Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information. Biological Psychiatry 2021, 91: 626-636. PMID: 34865855, PMCID: PMC8917986, DOI: 10.1016/j.biopsych.2021.09.020.Peer-Reviewed Original ResearchGenome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
Mullins N, Forstner AJ, O’Connell K, Coombes B, Coleman JRI, Qiao Z, Als TD, Bigdeli TB, Børte S, Bryois J, Charney AW, Drange OK, Gandal MJ, Hagenaars SP, Ikeda M, Kamitaki N, Kim M, Krebs K, Panagiotaropoulou G, Schilder BM, Sloofman LG, Steinberg S, Trubetskoy V, Winsvold BS, Won HH, Abramova L, Adorjan K, Agerbo E, Al Eissa M, Albani D, Alliey-Rodriguez N, Anjorin A, Antilla V, Antoniou A, Awasthi S, Baek JH, Bækvad-Hansen M, Bass N, Bauer M, Beins EC, Bergen SE, Birner A, Bøcker Pedersen C, Bøen E, Boks MP, Bosch R, Brum M, Brumpton BM, Brunkhorst-Kanaan N, Budde M, Bybjerg-Grauholm J, Byerley W, Cairns M, Casas M, Cervantes P, Clarke TK, Cruceanu C, Cuellar-Barboza A, Cunningham J, Curtis D, Czerski PM, Dale AM, Dalkner N, David FS, Degenhardt F, Djurovic S, Dobbyn AL, Douzenis A, Elvsåshagen T, Escott-Price V, Ferrier IN, Fiorentino A, Foroud TM, Forty L, Frank J, Frei O, Freimer NB, Frisén L, Gade K, Garnham J, Gelernter J, Giørtz Pedersen M, Gizer IR, Gordon SD, Gordon-Smith K, Greenwood TA, Grove J, Guzman-Parra J, Ha K, Haraldsson M, Hautzinger M, Heilbronner U, Hellgren D, Herms S, Hoffmann P, Holmans PA, Huckins L, Jamain S, Johnson JS, Kalman JL, Kamatani Y, Kennedy JL, Kittel-Schneider S, Knowles JA, Kogevinas M, Koromina M, Kranz TM, Kranzler HR, Kubo M, Kupka R, Kushner SA, Lavebratt C, Lawrence J, Leber M, Lee HJ, Lee PH, Levy SE, Lewis C, Liao C, Lucae S, Lundberg M, MacIntyre DJ, Magnusson SH, Maier W, Maihofer A, Malaspina D, Maratou E, Martinsson L, Mattheisen M, McCarroll SA, McGregor NW, McGuffin P, McKay JD, Medeiros H, Medland SE, Millischer V, Montgomery GW, Moran JL, Morris DW, Mühleisen TW, O’Brien N, O’Donovan C, Olde Loohuis LM, Oruc L, Papiol S, Pardiñas AF, Perry A, Pfennig A, Porichi E, Potash JB, Quested D, Raj T, Rapaport MH, DePaulo JR, Regeer EJ, Rice JP, Rivas F, Rivera M, Roth J, Roussos P, Ruderfer DM, Sánchez-Mora C, Schulte EC, Senner F, Sharp S, Shilling PD, Sigurdsson E, Sirignano L, Slaney C, Smeland OB, Smith DJ, Sobell JL, Søholm Hansen C, Soler Artigas M, Spijker AT, Stein DJ, Strauss JS, Świątkowska B, Terao C, Thorgeirsson TE, Toma C, Tooney P, Tsermpini EE, Vawter MP, Vedder H, Walters JTR, Witt SH, Xi S, Xu W, Yang JMK, Young AH, Young H, Zandi PP, Zhou H, Zillich L, Adolfsson R, Agartz I, Alda M, Alfredsson L, Babadjanova G, Backlund L, Baune B, Bellivier F, Bengesser S, Berrettini W, Blackwood D, Boehnke M, Børglum A, Breen G, Carr V, Catts S, Corvin A, Craddock N, Dannlowski U, Dikeos D, Esko T, Etain B, Ferentinos P, Frye M, Fullerton J, Gawlik M, Gershon E, Goes F, Green M, Grigoroiu-Serbanescu M, Hauser J, Henskens F, Hillert J, Hong K, Hougaard D, Hultman C, Hveem K, Iwata N, Jablensky A, Jones I, Jones L, Kahn R, Kelsoe J, Kirov G, Landén M, Leboyer M, Lewis C, Li Q, Lissowska J, Lochner C, Loughland C, Martin N, Mathews C, Mayoral F, McElroy S, McIntosh A, McMahon F, Melle I, Michie P, Milani L, Mitchell P, Morken G, Mors O, Mortensen P, Mowry B, Müller-Myhsok B, Myers R, Neale B, Nievergelt C, Nordentoft M, Nöthen M, O’Donovan M, Oedegaard K, Olsson T, Owen M, Paciga S, Pantelis C, Pato C, Pato M, Patrinos G, Perlis R, Posthuma D, Ramos-Quiroga J, Reif A, Reininghaus E, Ribasés M, Rietschel M, Ripke S, Rouleau G, Saito T, Schall U, Schalling M, Schofield P, Schulze T, Scott L, Scott R, Serretti A, Shannon Weickert C, Smoller J, Stefansson H, Stefansson K, Stordal E, Streit F, Sullivan P, Turecki G, Vaaler A, Vieta E, Vincent J, Waldman I, Weickert T, Werge T, Wray N, Zwart J, Biernacka J, Nurnberger J, Cichon S, Edenberg H, Stahl E, McQuillin A, Di Florio A, Ophoff R, Andreassen O. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nature Genetics 2021, 53: 817-829. PMID: 34002096, PMCID: PMC8192451, DOI: 10.1038/s41588-021-00857-4.Peer-Reviewed Original ResearchConceptsAssociation studiesQuantitative trait loci dataExpression quantitative trait loci (eQTL) dataGenome-wide association studiesBipolar disorder casesBrain-expressed genesWide association studyHeritable mental illnessSynaptic signaling pathwaysGenomic lociTargets of antipsychoticsLoci dataImperfect genetic correlationGene expressionSignaling pathwaysFunctional followGenesGenetic correlationsDruggable targetsSignal enrichmentEuropean ancestryLociBipolar disorder risk allelesNew insightsTherapeutic leads
2020
Characterizing the effect of background selection on the polygenicity of brain-related traits
Wendt FR, Pathak GA, Overstreet C, Tylee DS, Gelernter J, Atkinson EG, Polimanti R. Characterizing the effect of background selection on the polygenicity of brain-related traits. Genomics 2020, 113: 111-119. PMID: 33278486, PMCID: PMC7855394, DOI: 10.1016/j.ygeno.2020.11.032.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesBrain-related traitsGWAS of schizophreniaTrait-associated lociLocus effect sizesSubset of traitsGenotype networksGenetic architectureIntolerant regionsBrain-related phenotypesBackground selectionNatural selectionEvolutionary pressurePositive selectionSNP heritabilityLocal ancestryAssociation studiesTraitsFunctional significanceLociPolygenicityBinary annotationPhenotypeRisk allelesSize varianceExpanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits
Quach BC, Bray MJ, Gaddis NC, Liu M, Palviainen T, Minica CC, Zellers S, Sherva R, Aliev F, Nothnagel M, Young KA, Marks JA, Young H, Carnes MU, Guo Y, Waldrop A, Sey NYA, Landi MT, McNeil DW, Drichel D, Farrer LA, Markunas CA, Vink JM, Hottenga JJ, Iacono WG, Kranzler HR, Saccone NL, Neale MC, Madden P, Rietschel M, Marazita ML, McGue M, Won H, Winterer G, Grucza R, Dick DM, Gelernter J, Caporaso NE, Baker TB, Boomsma DI, Kaprio J, Hokanson JE, Vrieze S, Bierut LJ, Johnson EO, Hancock DB. Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits. Nature Communications 2020, 11: 5562. PMID: 33144568, PMCID: PMC7642344, DOI: 10.1038/s41467-020-19265-z.Peer-Reviewed Original ResearchConceptsGenome-wide significant lociGenome-wide association studiesNearby gene expressionExpression of genesSmoking traitsGenetic architectureSignificant lociGenetic variationMultiple traitsGene expressionAssociation studiesLociTraitsGenetic knowledgeComposite phenotypeUK BiobankExpressionTENM2GNAI1GenesGeneticsVariantsPhenotype