2024
Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder
Nievergelt C, Maihofer A, Atkinson E, Chen C, Choi K, Coleman J, Daskalakis N, Duncan L, Polimanti R, Aaronson C, Amstadter A, Andersen S, Andreassen O, Arbisi P, Ashley-Koch A, Austin S, Avdibegoviç E, Babić D, Bacanu S, Baker D, Batzler A, Beckham J, Belangero S, Benjet C, Bergner C, Bierer L, Biernacka J, Bierut L, Bisson J, Boks M, Bolger E, Brandolino A, Breen G, Bressan R, Bryant R, Bustamante A, Bybjerg-Grauholm J, Bækvad-Hansen M, Børglum A, Børte S, Cahn L, Calabrese J, Caldas-de-Almeida J, Chatzinakos C, Cheema S, Clouston S, Colodro-Conde L, Coombes B, Cruz-Fuentes C, Dale A, Dalvie S, Davis L, Deckert J, Delahanty D, Dennis M, Desarnaud F, DiPietro C, Disner S, Docherty A, Domschke K, Dyb G, Kulenović A, Edenberg H, Evans A, Fabbri C, Fani N, Farrer L, Feder A, Feeny N, Flory J, Forbes D, Franz C, Galea S, Garrett M, Gelaye B, Gelernter J, Geuze E, Gillespie C, Goleva S, Gordon S, Goçi A, Grasser L, Guindalini C, Haas M, Hagenaars S, Hauser M, Heath A, Hemmings S, Hesselbrock V, Hickie I, Hogan K, Hougaard D, Huang H, Huckins L, Hveem K, Jakovljević M, Javanbakht A, Jenkins G, Johnson J, Jones I, Jovanovic T, Karstoft K, Kaufman M, Kennedy J, Kessler R, Khan A, Kimbrel N, King A, Koen N, Kotov R, Kranzler H, Krebs K, Kremen W, Kuan P, Lawford B, Lebois L, Lehto K, Levey D, Lewis C, Liberzon I, Linnstaedt S, Logue M, Lori A, Lu Y, Luft B, Lupton M, Luykx J, Makotkine I, Maples-Keller J, Marchese S, Marmar C, Martin N, Martínez-Levy G, McAloney K, McFarlane A, McLaughlin K, McLean S, Medland S, Mehta D, Meyers J, Michopoulos V, Mikita E, Milani L, Milberg W, Miller M, Morey R, Morris C, Mors O, Mortensen P, Mufford M, Nelson E, Nordentoft M, Norman S, Nugent N, O’Donnell M, Orcutt H, Pan P, Panizzon M, Pathak G, Peters E, Peterson A, Peverill M, Pietrzak R, Polusny M, Porjesz B, Powers A, Qin X, Ratanatharathorn A, Risbrough V, Roberts A, Rothbaum A, Rothbaum B, Roy-Byrne P, Ruggiero K, Rung A, Runz H, Rutten B, de Viteri S, Salum G, Sampson L, Sanchez S, Santoro M, Seah C, Seedat S, Seng J, Shabalin A, Sheerin C, Silove D, Smith A, Smoller J, Sponheim S, Stein D, Stensland S, Stevens J, Sumner J, Teicher M, Thompson W, Tiwari A, Trapido E, Uddin M, Ursano R, Valdimarsdóttir U, Van Hooff M, Vermetten E, Vinkers C, Voisey J, Wang Y, Wang Z, Waszczuk M, Weber H, Wendt F, Werge T, Williams M, Williamson D, Winsvold B, Winternitz S, Wolf C, Wolf E, Xia Y, Xiong Y, Yehuda R, Young K, Young R, Zai C, Zai G, Zervas M, Zhao H, Zoellner L, Zwart J, deRoon-Cassini T, van Rooij S, van den Heuvel L, Stein M, Ressler K, Koenen K. Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder. Nature Genetics 2024, 56: 792-808. PMID: 38637617, PMCID: PMC11396662, DOI: 10.1038/s41588-024-01707-9.Peer-Reviewed Original ResearchConceptsMeta-analysis of genome-wide association studiesGenome-wide significant lociMulti-ancestry meta-analysisGenome-wide association analysisGenome-wide association studiesIndividuals of European ancestryPotential causal genesNative American ancestryMulti-omics approachPost-traumatic stress disorderAdmixed individualsSignificant lociRisk lociCausal genesAssociation studiesAssociation analysisFunctional genesTranscription factorsGenetic studiesAmerican ancestryEuropean ancestryAxon guidanceSynaptic structureLociGenes
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 smokingMulti‐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
2020
A large-scale genome-wide association study meta-analysis of cannabis use disorder
Johnson EC, Demontis D, Thorgeirsson TE, Walters RK, Polimanti R, Hatoum AS, Sanchez-Roige S, Paul SE, Wendt FR, Clarke TK, Lai D, Reginsson GW, Zhou H, He J, Baranger DAA, Gudbjartsson DF, Wedow R, Adkins DE, Adkins AE, Alexander J, Bacanu SA, Bigdeli TB, Boden J, Brown SA, Bucholz KK, Bybjerg-Grauholm J, Corley RP, Degenhardt L, Dick DM, Domingue BW, Fox L, Goate AM, Gordon SD, Hack LM, Hancock DB, Hartz SM, Hickie IB, Hougaard DM, Krauter K, Lind PA, McClintick JN, McQueen MB, Meyers JL, Montgomery GW, Mors O, Mortensen PB, Nordentoft M, Pearson JF, Peterson RE, Reynolds MD, Rice JP, Runarsdottir V, Saccone NL, Sherva R, Silberg JL, Tarter RE, Tyrfingsson T, Wall TL, Webb BT, Werge T, Wetherill L, Wright MJ, Zellers S, Adams MJ, Bierut LJ, Boardman JD, Copeland WE, Farrer LA, Foroud TM, Gillespie NA, Grucza RA, Harris KM, Heath AC, Hesselbrock V, Hewitt JK, Hopfer CJ, Horwood J, Iacono WG, Johnson EO, Kendler KS, Kennedy MA, Kranzler HR, Madden PAF, Maes HH, Maher BS, Martin NG, McGue M, McIntosh AM, Medland SE, Nelson EC, Porjesz B, Riley BP, Stallings MC, Vanyukov MM, Vrieze S, Workgroup P, Walters R, Polimanti R, Johnson E, McClintick J, Hatoum A, He J, Wendt F, Zhou H, Adams M, Adkins A, Aliev F, Bacanu S, Batzler A, Bertelsen S, Biernacka J, Bigdeli T, Chen L, Clarke T, Chou Y, Degenhardt F, Docherty A, Edwards A, Fontanillas P, Foo J, Fox L, Frank J, Giegling I, Gordon S, Hack L, Hartmann A, Hartz S, Heilmann-Heimbach S, Herms S, Hodgkinson C, Hoffman P, Hottenga J, Kennedy M, Alanne-Kinnunen M, Konte B, Lahti J, Lahti-Pulkkinen M, Lai D, Ligthart L, Loukola A, Maher B, Mbarek H, McIntosh A, McQueen M, Meyers J, Milaneschi Y, Palviainen T, Pearson J, Peterson R, Ripatti S, Ryu E, Saccone N, Salvatore J, Sanchez-Roige S, Schwandt M, Sherva R, Streit F, Strohmaier J, Thomas N, Wang J, Webb B, Wedow R, Wetherill L, Wills A, Boardman J, Chen D, Choi D, Copeland W, Culverhouse R, Dahmen N, Degenhardt L, Domingue B, Elson S, Frye M, Gäbel W, Hayward C, Ising M, Keyes M, Kiefer F, Kramer J, Kuperman S, Lucae S, Lynskey M, Maier W, Mann K, Männistö S, Müller-Myhsok B, Murray A, Nurnberger J, Palotie A, Preuss U, Räikkönen K, Reynolds M, Ridinger M, Scherbaum N, Schuckit M, Soyka M, Treutlein J, Witt S, Wodarz N, Zill P, Adkins D, Boden J, Boomsma D, Bierut L, Brown S, Bucholz K, Cichon S, Costello E, de Wit H, Diazgranados N, Dick D, Eriksson J, Farrer L, Foroud T, Gillespie N, Goate A, Goldman D, Grucza R, Hancock D, Harris K, Heath A, Hesselbrock V, Hewitt J, Hopfer C, Horwood J, Iacono W, Johnson E, Kaprio J, Karpyak V, Kendler K, Kranzler H, Krauter K, Lichtenstein P, Lind P, McGue M, MacKillop J, Madden P, Maes H, Magnusson P, Martin N, Medland S, Montgomery G, Nelson E, Nöthen M, Palmer A, Pederson N, Penninx B, Porjesz B, Rice J, Rietschel M, Riley B, Rose R, Rujescu D, Shen P, Silberg J, Stallings M, Tarter R, Vanyukov M, Vrieze S, Wall T, Whitfield J, Zhao H, Neale B, Gelernter J, Edenberg H, Agrawal A, Davis L, Bogdan R, Gelernter J, Edenberg H, Stefansson K, Børglum A, Agrawal A. A large-scale genome-wide association study meta-analysis of cannabis use disorder. The Lancet Psychiatry 2020, 7: 1032-1045. PMID: 33096046, PMCID: PMC7674631, DOI: 10.1016/s2215-0366(20)30339-4.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesGenome-wide significant lociLarge-scale genome-wide association studiesGenetic correlationsChromosome 7 locusTraits of interestLarge genome-wide association studiesLinkage disequilibrium score regressionChromosome 8 locusDifferent genetic underpinningsDifferent genetic correlationsWellcome Trust Case Control ConsortiumDisequilibrium score regressionNovel genetic variantsStrong genetic componentSignificant lociGenetic lociGenetic underpinningsGenetic componentLociScore regressionGenetic variantsGenetic overlapIntegrative sequencing
2019
International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci
Nievergelt CM, Maihofer AX, Klengel T, Atkinson EG, Chen CY, Choi KW, Coleman JRI, Dalvie S, Duncan LE, Gelernter J, Levey DF, Logue MW, Polimanti R, Provost AC, Ratanatharathorn A, Stein MB, Torres K, Aiello AE, Almli LM, Amstadter AB, Andersen SB, Andreassen OA, Arbisi PA, Ashley-Koch AE, Austin SB, Avdibegovic E, Babić D, Bækvad-Hansen M, Baker DG, Beckham JC, Bierut LJ, Bisson JI, Boks MP, Bolger EA, Børglum AD, Bradley B, Brashear M, Breen G, Bryant RA, Bustamante AC, Bybjerg-Grauholm J, Calabrese JR, Caldas- de- Almeida J, Dale AM, Daly MJ, Daskalakis NP, Deckert J, Delahanty DL, Dennis MF, Disner SG, Domschke K, Dzubur-Kulenovic A, Erbes CR, Evans A, Farrer LA, Feeny NC, Flory JD, Forbes D, Franz CE, Galea S, Garrett ME, Gelaye B, Geuze E, Gillespie C, Uka AG, Gordon SD, Guffanti G, Hammamieh R, Harnal S, Hauser MA, Heath AC, Hemmings SMJ, Hougaard DM, Jakovljevic M, Jett M, Johnson EO, Jones I, Jovanovic T, Qin XJ, Junglen AG, Karstoft KI, Kaufman ML, Kessler RC, Khan A, Kimbrel NA, King AP, Koen N, Kranzler HR, Kremen WS, Lawford BR, Lebois LAM, Lewis CE, Linnstaedt SD, Lori A, Lugonja B, Luykx JJ, Lyons MJ, Maples-Keller J, Marmar C, Martin AR, Martin NG, Maurer D, Mavissakalian MR, McFarlane A, McGlinchey RE, McLaughlin KA, McLean SA, McLeay S, Mehta D, Milberg WP, Miller MW, Morey RA, Morris CP, Mors O, Mortensen PB, Neale BM, 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, Ripke S, Risbrough VB, Roberts AL, Rothbaum AO, Rothbaum BO, Roy-Byrne P, Ruggiero K, 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, Sumner JA, 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, Wolff JD, Yehuda R, Young RM, Young KA, Zhao H, Zoellner LA, Liberzon I, Ressler KJ, Haas M, Koenen KC. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci. Nature Communications 2019, 10: 4558. PMID: 31594949, PMCID: PMC6783435, DOI: 10.1038/s41467-019-12576-w.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesDisease genesAssociation studiesGenome-wide significant lociAfrican-ancestry analysesNon-coding RNAsGenetic risk lociParkinson's disease genesEuropean ancestry populationsNovel genesSignificant lociGenetic variationSpecific lociRisk lociAdditional lociLociAncestry populationsCommon variantsHeritability estimatesGenesGWASRNABiologySNPsPARK2Genome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci
Gelernter J, Sun N, Polimanti R, Pietrzak RH, Levey DF, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M, Cheung KH, Li Y, Rajeevan N, Sayward F, Harrington K, Chen Q, Cho K, Honerlaw J, Pyarajan S, Lencz T, Quaden R, Shi Y, Hunter-Zinck H, Gaziano JM, Kranzler HR, Concato J, Zhao H, Stein MB, Program D, Program M. Genome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci. Biological Psychiatry 2019, 86: 365-376. PMID: 31151762, PMCID: PMC6919570, DOI: 10.1016/j.biopsych.2019.03.984.Peer-Reviewed Original ResearchConceptsAdditional genome-wide significant lociRisk lociWide association study (GWAS) analysisAssociation studiesGenome-wide significant lociGenome-wide association studiesGenetic correlationsWide association studyNovel risk lociAlcohol-related traitsStrong statistical supportSmoking-related traitsAdditional genomesSignificant lociPancreatic delta cellsChromosome 4Chromosome 11Protein productsChromosome 8Quantitative phenotypesMillion Veteran ProgramVeterans Affairs Million Veteran ProgramLociCell typesChromosome 17Genome-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
2013
Linkage Disequilibrium and Haplotype Analysis of the ATP7B Gene in Alzheimer's Disease
Squitti R, Polimanti R, Bucossi S, Ventriglia M, Mariani S, Manfellotto D, Vernieri F, Cassetta E, Ursini F, Rossini PM. Linkage Disequilibrium and Haplotype Analysis of the ATP7B Gene in Alzheimer's Disease. Rejuvenation Research 2013, 16: 3-10. PMID: 22950421, PMCID: PMC3582274, DOI: 10.1089/rej.2012.1357.Peer-Reviewed Original ResearchConceptsCopper-binding domainSingle nucleotide polymorphismsInformative single nucleotide polymorphismsAssociation studiesLD blocksRole of ATP7BWide association studyLinkage disequilibrium analysisGenetic structureVariants/haplotypesGenetic association analysisTransmembrane domainSignificant lociGene sequencesGenetic association studiesATP7B geneGene regionAssociation analysisGenesDisequilibrium analysisLinkage disequilibriumNovel insightsCopper dyshomeostasisStrong LDMultiple testing correction