2023
Whole-Exome Sequencing Analyses Support a Role of Vitamin D Metabolism in Ischemic Stroke
Xie Y, Acosta J, Ye Y, Demarais Z, Conlon C, Chen M, Zhao H, Falcone G. Whole-Exome Sequencing Analyses Support a Role of Vitamin D Metabolism in Ischemic Stroke. Stroke 2023, 54: 800-809. PMID: 36762557, PMCID: PMC10467223, DOI: 10.1161/strokeaha.122.040883.Peer-Reviewed Original ResearchConceptsGene-based testingRare genetic variationGene-based analysisGenetic variationAssociation studiesGenome-wide association studiesSingle-variant association analysisWide significance levelSusceptibility risk lociWide association studyDeleterious missense variantsMissense rare variantsBonferroni-corrected thresholdWhole-exome sequencing dataRare variantsSingle variant analysisHeritable traitRisk lociExome-wide studySequencing dataExome sequencing analysisAssociation analysisSequencing analysisMissense variantsTraits
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 Determinants of Risk, Severity, and Outcome in Intracerebral Hemorrhage
Falcone GJ, Rosand J. Genetic Determinants of Risk, Severity, and Outcome in Intracerebral Hemorrhage. Seminars In Neurology 2016, 36: 298-305. PMID: 27214705, DOI: 10.1055/s-0036-1582134.Peer-Reviewed Original ResearchConceptsGenetic discoveriesNew biological mechanismsRecent genetic discoveriesGenomic analysisGenetic variationGenetic analysisGenetic determinantsBiological mechanismsIntracerebral hemorrhageInnovative therapeutic interventionsTranslational research effortsPowerful toolDiscoveryCerebral small vessel diseaseTherapeutic interventionsLow-frequency and common genetic variation in ischemic stroke
Malik R, Traylor M, Pulit SL, Bevan S, Hopewell JC, Holliday EG, Zhao W, Abrantes P, Amouyel P, Attia JR, Battey TW, Berger K, Boncoraglio GB, Chauhan G, Cheng YC, Chen WM, Clarke R, Cotlarciuc I, Debette S, Falcone GJ, Ferro JM, Gamble DM, Ilinca A, Kittner SJ, Kourkoulis CE, Lemmens R, Levi CR, Lichtner P, Lindgren A, Liu J, Meschia JF, Mitchell BD, Oliveira SA, Pera J, Reiner AP, Rothwell PM, Sharma P, Slowik A, Sudlow CL, Tatlisumak T, Thijs V, Vicente AM, Woo D, Seshadri S, Saleheen D, Rosand J, Markus HS, Worrall BB, Dichgans M. Low-frequency and common genetic variation in ischemic stroke. Neurology 2016, 86: 1217-1226. PMID: 26935894, PMCID: PMC4818561, DOI: 10.1212/wnl.0000000000002528.Peer-Reviewed Original ResearchConceptsIndividual genome-wide association studiesLow-frequency genetic variantsGenome-wide association studiesCommon genetic variationHigh-frequency variantsGenomes Phase ILow-frequency variantsGenetic variationAssociation studiesFrequency variantsSignificant enrichmentGenetic variantsAllele frequenciesPITX2Rare variantsSouth Asian sampleWider significanceVariantsEnrichmentLociDiscovery phaseHDAC9P-value distributionsHeritabilityZFHX3
2014
Current concepts and clinical applications of stroke genetics
Falcone GJ, Malik R, Dichgans M, Rosand J. Current concepts and clinical applications of stroke genetics. The Lancet Neurology 2014, 13: 405-418. PMID: 24646874, DOI: 10.1016/s1474-4422(14)70029-8.Peer-Reviewed Original Research
2013
Heritability Estimates Identify a Substantial Genetic Contribution to Risk and Outcome of Intracerebral Hemorrhage
Devan WJ, Falcone GJ, Anderson CD, Jagiella JM, Schmidt H, Hansen BM, Jimenez-Conde J, Giralt-Steinhauer E, Cuadrado-Godia E, Soriano C, Ayres AM, Schwab K, Kassis SB, Valant V, Pera J, Urbanik A, Viswanathan A, Rost NS, Goldstein JN, Freudenberger P, Stögerer EM, Norrving B, Tirschwell DL, Selim M, Brown DL, Silliman SL, Worrall BB, Meschia JF, Kidwell CS, Montaner J, Fernandez-Cadenas I, Delgado P, Greenberg SM, Roquer J, Lindgren A, Slowik A, Schmidt R, Woo D, Rosand J, Biffi A. Heritability Estimates Identify a Substantial Genetic Contribution to Risk and Outcome of Intracerebral Hemorrhage. Stroke 2013, 44: 1578-1583. PMID: 23559261, PMCID: PMC3684199, DOI: 10.1161/strokeaha.111.000089.Peer-Reviewed Original ResearchConceptsGenetic variationGenome-wide genotype dataGenome-wide dataGenetic contributionHeritability estimatesPedigree-based studiesSubstantial genetic contributionFamily-based dataAdditional lociGenotype dataRisk variantsGenetic variantsHeritabilityGenetic influencesHeritability estimationProportion of variationNovel analytic toolGenetic risk factorsPhenotypeSubstantial roleUnrelated subjectsGenomeGenesLociVariants