2018
17p12 Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage
Marini S, Devan WJ, Radmanesh F, Miyares L, Poterba T, Hansen BM, Norrving B, Jimenez-Conde J, Giralt-Steinhauer E, Elosua R, Cuadrado-Godia E, Soriano C, Roquer J, Kourkoulis CE, Ayres AM, Schwab K, Tirschwell DL, Selim M, Brown DL, Silliman SL, Worrall BB, Meschia JF, Kidwell CS, Montaner J, Fernandez-Cadenas I, Delgado P, Greenberg SM, Lindgren A, Matouk C, Sheth KN, Woo D, Anderson CD, Rosand J, Falcone GJ. 17p12 Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage. Stroke 2018, 49: 1618-1625. PMID: 29915124, PMCID: PMC6085089, DOI: 10.1161/strokeaha.117.020091.Peer-Reviewed Original ResearchConceptsAssociation studiesGenome-wide association studiesNumerous copy number variantsSusceptibility risk lociWide association studyNovel biological pathwaysGenomic regionsIntergenic regionCopy number variantsRisk lociBiological pathwaysSusceptibility lociAssociation testingGenetic variantsNumber variantsEuropean ancestryLociReplicationDiscovery phaseVariantsAncestryImportant determinantPathwayTranslational studiesQuality controlMultiancestry 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 outcomesLow-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
2015
Rare Coding Variation and Risk of Intracerebral Hemorrhage
Radmanesh F, Falcone GJ, Anderson CD, McWilliams D, Devan WJ, Brown WM, Battey TW, Ayres AM, Raffeld MR, Schwab K, Sun G, Deka R, Viswanathan A, Goldstein JN, Greenberg SM, Tirschwell DL, Silliman SL, Selim M, Meschia JF, Brown DL, Worrall BB, Langefeld CD, Woo D, Rosand J. Rare Coding Variation and Risk of Intracerebral Hemorrhage. Stroke 2015, 46: 2299-2301. PMID: 26111891, PMCID: PMC4519408, DOI: 10.1161/strokeaha.115.009838.Peer-Reviewed Original ResearchConceptsGenome-wide significance levelRare coding variationsGene-based association testingSusceptibility lociGene-based associationRare Coding VariantsGenome-wide significanceIllumina HumanExome BeadChipGenetic susceptibility lociSubstantial genetic componentCoding variationsChromosome 19q13APOE epsilon allelesHumanExome BeadChipGenetic componentCoding variantAssociation testingLociCommon variantsEpsilon allelesLarge effectVariantsBeadChipGenesTOMM40
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