2018
Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A, Rutten-Jacobs L, Giese AK, van der Laan SW, Gretarsdottir S, Anderson CD, Chong M, Adams HHH, Ago T, Almgren P, Amouyel P, Ay H, Bartz TM, Benavente OR, Bevan S, Boncoraglio GB, Brown RD, Butterworth AS, Carrera C, Carty CL, Chasman DI, Chen WM, Cole JW, Correa A, Cotlarciuc I, Cruchaga C, Danesh J, de Bakker PIW, DeStefano AL, den Hoed M, Duan Q, Engelter ST, Falcone GJ, Gottesman RF, Grewal RP, Gudnason V, Gustafsson S, Haessler J, Harris TB, Hassan A, Havulinna AS, Heckbert SR, Holliday EG, Howard G, Hsu FC, Hyacinth HI, Ikram MA, Ingelsson E, Irvin MR, Jian X, Jiménez-Conde J, Johnson JA, Jukema JW, Kanai M, Keene KL, Kissela BM, Kleindorfer DO, Kooperberg C, Kubo M, Lange LA, Langefeld CD, Langenberg C, Launer LJ, Lee JM, Lemmens R, Leys D, Lewis CM, Lin WY, Lindgren AG, Lorentzen E, Magnusson PK, Maguire J, Manichaikul A, McArdle PF, Meschia JF, Mitchell BD, Mosley TH, Nalls MA, Ninomiya T, O’Donnell M, Psaty BM, Pulit SL, Rannikmäe K, Reiner AP, Rexrode KM, Rice K, Rich SS, Ridker PM, Rost NS, Rothwell PM, Rotter JI, Rundek T, Sacco RL, Sakaue S, Sale MM, Salomaa V, Sapkota BR, Schmidt R, Schmidt CO, Schminke U, Sharma P, Slowik A, Sudlow CLM, Tanislav C, Tatlisumak T, Taylor KD, Thijs VNS, Thorleifsson G, Thorsteinsdottir U, Tiedt S, Trompet S, Tzourio C, van Duijn CM, Walters M, Wareham NJ, Wassertheil-Smoller S, Wilson JG, Wiggins KL, Yang Q, Yusuf S, Bis J, Pastinen T, Ruusalepp A, Schadt E, Koplev S, Björkegren J, Codoni V, Civelek M, Smith N, Trégouët D, Christophersen I, Roselli C, Lubitz S, Ellinor P, Tai E, Kooner J, Kato N, He J, van der Harst P, Elliott P, Chambers J, Takeuchi F, Johnson A, Sanghera D, Melander O, Jern C, Strbian D, Fernandez-Cadenas I, Longstreth W, Rolfs A, Hata J, Woo D, Rosand J, Pare G, Hopewell J, Saleheen D, Stefansson K, Worrall B, Kittner S, Seshadri S, Fornage M, Markus H, Howson J, Kamatani Y, Debette S, Dichgans M. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nature Genetics 2018, 50: 524-537. PMID: 29531354, PMCID: PMC5968830, DOI: 10.1038/s41588-018-0058-3.Peer-Reviewed Original ResearchConceptsStroke risk lociRisk lociGenome-wide association studiesNew susceptibility lociGenetic variationIndividual lociVascular traitsBioinformatics analysisAssociation studiesCardiac traitsSusceptibility lociDrug targetsLociRisk variantsScore regressionGenesFunctional datasetsTraitsGenetic risk scoreDistinct associationsPathwayVariantsTarget
2016
Genetic variants in CETP increase risk of intracerebral hemorrhage
Anderson CD, Falcone GJ, Phuah C, Radmanesh F, Brouwers HB, Battey TW, Biffi A, Peloso GM, Liu DJ, Ayres AM, Goldstein JN, Viswanathan A, Greenberg SM, Selim M, Meschia JF, Brown DL, Worrall BB, Silliman SL, Tirschwell DL, Flaherty ML, Kraft P, Jagiella JM, Schmidt H, Hansen BM, Jimenez‐Conde J, Giralt‐Steinhauer E, Elosua R, Cuadrado‐Godia E, Soriano C, van Nieuwenhuizen K, Klijn CJ, Rannikmae K, Samarasekera N, Salman R, Sudlow CL, Deary IJ, Morotti A, Pezzini A, Pera J, Urbanik A, Pichler A, Enzinger C, Norrving B, Montaner J, Fernandez‐Cadenas I, Delgado P, Roquer J, Lindgren A, Slowik A, Schmidt R, Kidwell CS, Kittner SJ, Waddy SP, Langefeld CD, Abecasis G, Willer CJ, Kathiresan S, Woo D, Rosand J, Consortium O. Genetic variants in CETP increase risk of intracerebral hemorrhage. Annals Of Neurology 2016, 80: 730-740. PMID: 27717122, PMCID: PMC5115931, DOI: 10.1002/ana.24780.Peer-Reviewed Original ResearchConceptsGenetic variantsCandidate gene analysisDNA sequence variantsGlobal Lipids Genetics ConsortiumDNA sequencesOngoing therapeutic developmentsSequence variantsIndependent variantsNominal associationCETP locusGenetics ConsortiumEuropean ancestryCETP variantsLociTherapeutic developmentVariantsGenetic risk scoreCETPDiscovery cohortGenetic scoreAncestryReplicationSequenceAnn NeurolAdverse cerebrovascular outcomes
2014
Dopamine Genetic Risk Score Predicts Depressive Symptoms in Healthy Adults and Adults with Depression
Pearson-Fuhrhop KM, Dunn EC, Mortero S, Devan WJ, Falcone GJ, Lee P, Holmes AJ, Hollinshead MO, Roffman JL, Smoller JW, Rosand J, Cramer SC. Dopamine Genetic Risk Score Predicts Depressive Symptoms in Healthy Adults and Adults with Depression. PLOS ONE 2014, 9: e93772. PMID: 24834916, PMCID: PMC4023941, DOI: 10.1371/journal.pone.0093772.Peer-Reviewed Original ResearchConceptsGenetic risk scoreRisk scoreHealthy adult participantsDepressive symptomatologyAdult participantsPathophysiology of depressionDopamine receptor bindingSynaptic dopamine availabilityDiscovery sampleReplication sampleDopamine-related genesDopamine metabolismMonoamine neurotransmissionDepressive symptomsDopamine neurotransmissionHealthy individualsHealthy adultsFunctional polymorphismsHuman disabilityDopamine availabilityReceptor bindingDepressionEtiologic insightsAdultsFurther studies
2013
Burden of Blood Pressure–Related Alleles Is Associated With Larger Hematoma Volume and Worse Outcome in Intracerebral Hemorrhage
Falcone GJ, Biffi A, Devan WJ, Brouwers HB, Anderson CD, Valant V, Ayres AM, Schwab K, Rost NS, Goldstein JN, Viswanathan A, Greenberg SM, Selim M, Meschia JF, Brown DL, Worrall BB, Silliman SL, Tirschwell DL, Rosand J. Burden of Blood Pressure–Related Alleles Is Associated With Larger Hematoma Volume and Worse Outcome in Intracerebral Hemorrhage. Stroke 2013, 44: 321-326. PMID: 23321443, PMCID: PMC3560332, DOI: 10.1161/strokeaha.112.675181.Peer-Reviewed Original ResearchConceptsPoor clinical outcomeBaseline hematoma volumeIntracerebral hemorrhageClinical outcomesHematoma volumeGenetic risk scoreBlood pressureICH volumeRisk scoreHypertension-related end-organ damageRisk of ICHAdmission ICH volumeEnd-organ damageLarger hematoma volumeSupratentorial intracerebral hemorrhageHigh blood pressureCerebral small vesselsDeep intracerebral hemorrhageSmall vesselsSingle nucleotide polymorphismsMultivariate regression analysisProgressive diseaseProspective studyAcute manifestationsWorse outcomes
2012
Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage
Falcone GJ, Biffi A, Devan WJ, Jagiella JM, Schmidt H, Kissela B, Hansen BM, Jimenez-Conde J, Giralt-Steinhauer E, Elosua R, Cuadrado-Godia E, Soriano C, Ayres AM, Schwab K, Pera J, Urbanik A, Rost NS, Goldstein JN, Viswanathan A, Pichler A, Enzinger C, Norrving B, Tirschwell DL, Selim M, Brown DL, Silliman SL, Worrall BB, Meschia JF, Kidwell CS, Montaner J, Fernandez-Cadenas I, Delgado P, Broderick JP, Greenberg SM, Roquer J, Lindgren A, Slowik A, Schmidt R, Flaherty ML, Kleindorfer DO, Langefeld CD, Woo D, Rosand J. Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage. Stroke 2012, 43: 2877-2883. PMID: 22933587, PMCID: PMC3479325, DOI: 10.1161/strokeaha.112.659755.Peer-Reviewed Original ResearchConceptsRisk of ICHBlood pressure levelsIntracerebral hemorrhageGenetic risk scoreUnweighted genetic risk scoreRisk scoreProspective multicenter case-control studyMulticenter case-control studyHistory of hypertensionLobar intracerebral hemorrhageDeep intracerebral hemorrhagePotent risk factorCase-control studyLogistic regression modelsControl subjectsRisk factorsICH casesHypertensionIncrease riskCumulative burden