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RESEARCH PRODUCT

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Philipp S. WildFlorian ErnstJan LüdemannJerome I. RotterBraxton D. MitchellAaron IsaacsJames F. WilsonLeena PeltonenLeena PeltonenVijay NambiVijay NambiMika KähönenTamara B. HarrisJoseph F. PolakHenry VölzkeRavi Kumar ChilukotiJoshua C. BisUlf SchminkeNora FranceschiniKari E. NorthStefan BlankenbergNorman KloppJorma ViikariJennifer E. HuffmanThomas MünzelMatthias SitzerJoachim ThieryLenore J. LaunerEdward G. LakattaSerkalem DemissieCornelia M. Van DuijnH.-erich WichmannSerena SannaWendy S. PostDaniel H. O'learyRalph B. D'agostinoPhilip A. WolfPhilip A. WolfAndré G. UitterlindenOlli T. RaitakariThor AspelundTanja ZellerSteve BevanJochen SeisslerAfshin ParsaDavid CouperTerho LehtimäkiChristopher J. O'donnellChristopher J. O'donnellGeorg HomuthHelena SchmidtEva Maria StoegererXia LiGianluca UsalaWolfgang RathmannKent D. TaylorArne SchillertCharles C. WhiteKatja PetrovicReinhold SchmidtFernando RivadeneiraGudny EiriksdottirKenneth RiceAngelo ScuteriL. Adrienne CupplesL. Adrienne CupplesEran HalperinEran HalperinAlbert HofmanMarcus DörrAlbert V. SmithAbbas DehghanAlan R. ShuldinerAlan R. ShuldinerBolli ThorssonAnne B. NewmanChrista MeisingerGonçalo R. AbecasisJens BaumertGerardo HeissMarco OrruSekar KathiresanSekar KathiresanRenate B. SchnabelMuredach P. ReillyHugh S. MarkusCaroline S. FoxCaroline S. FoxChristie M. BallantyneAndreas ZieglerWolfgang KoenigMaryam KavousiVilmundur GudnasonCaroline HaywardEric BoerwinkleBen A. OostraJacqueline C.m. WittemanSusan R. HeckbertSusan R. HeckbertThomas IlligYu-ching ChengManuela UdaBruce M. PsatyBruce M. Psaty

subject

AgingMultifunction cardiogramGenome-wide association studyDiseaseCoronary Artery Disease030204 cardiovascular system & hematologyCarotid Intima-Media ThicknessCoronary artery diseaseCohort Studies0302 clinical medicinecardiovascular diseaseRisk FactorsAging/geneticsgeneticsMyocardial infarctionEuropean Continental Ancestry Group/geneticsriskPlaque0303 health scienceseducation.field_of_studyGenomeCoronary Artery Disease/geneticsHeartSingle NucleotidePlaque Atherosclerotic/geneticsMiddle AgedPlaque Atherosclerotic3. Good healthPhenotypeHeart/physiopathologyCardiologyHumanAdultmedicine.medical_specialtygenetic epidemiologyGenotypesubclinical atherosclerosisPopulationSingle-nucleotide polymorphismBiologyPolymorphism Single NucleotideWhite PeopleArticle03 medical and health sciencesSDG 3 - Good Health and Well-beingInternal medicinemedicinecohort studyHumanscarotid intima media thicknessGenetic Predisposition to DiseasePolymorphismeducation030304 developmental biologyAgedAtherosclerotic/geneticsGenome Humanmedicine.diseaseAtherosclerosismeta-analysisAtherosclerosis/geneticsIntima-media thicknessGenetic LociGenome-Wide Association Study

description

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.

yearjournalcountryeditionlanguage
2011-09-11
10.1038/ng.920https://hdl.handle.net/20.500.11820/83ad794a-0341-4c60-94c7-9cd37595774c