title: Impact of carotid atherosclerosis loci on cardiovascular events.
abstract: BACKGROUND
  Genome-wide association studies (GWAS) have identified six single-nucleotide polymorphisms (SNPs) related to carotid intima media thickness (cIMT) or plaque. However, whether these loci relate to other vascular diseases and subsequent vascular events is unclear.
  
  
  RESULTS
  We tested six SNPs (rs4888378, rs11781551, rs445925, rs6601530, rs17398575 and rs1878406) for association with subclinical atherosclerotic measures (cIMT, plaque presence and ankle-brachial index), as well as ischemic stroke, abdominal aortic aneurysm, peripheral or coronary artery disease (CAD) in the Second Manifestations of ARTerial disease (SMART) cohort. Four SNPs were associated with cIMT and two with plaque (p < 0.05). One SNP was also significantly associated to CAD (rs1878406, OR = 1.24, 95% CI = 1.08-1.42, p = 2 × 10(-3)). A genetic risk score (GRS) based on the cIMT-related SNPs was associated to increased risk of cIMT itself (p = 1 × 10(-3)), but not to other secondary outcomes or vascular events during follow-up (p = 0.86).
  
  
  CONCLUSIONS
  In addition to replicating previously published associations for cIMT, we confirmed a nominally significant effect between the GRS and cIMT.
authors.affiliation: Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands; CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil. Electronic address: D.Hemerich@umcutrecht.nl.
authors.forename: Daiane
authors.initials: D
authors.lastname: Hemerich
authors.affiliation: Laboratory of Experimental Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Sander W
authors.initials: SW
authors.lastname: van der Laan
authors.affiliation: Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Vinicius
authors.initials: V
authors.lastname: Tragante
authors.affiliation: Laboratory of Experimental Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
authors.forename: Hester M
authors.initials: HM
authors.lastname: den Ruijter
authors.affiliation: Department of Vascular Surgery, Division of Surgical Specialties, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: de Borst
authors.affiliation: Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands; Laboratory of Clinical Chemistry and Hematology, Division Laboratories and Pharmacy, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.affiliation: Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.affiliation: Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands; Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom. Electronic address: F.W.Asselbergs@umcutrecht.nl.
authors.forename: Folkert W
authors.initials: FW
authors.lastname: Asselbergs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055109:Ankle Brachial Index; D017544:Aortic Aneurysm, Abdominal / Q000175:diagnosis / Q000235:genetics; D002545:Brain Ischemia / Q000175:diagnosis / Q000235:genetics; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000175:diagnosis / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000235:genetics; D055815:Young Adult
chemical_list: D005819:Genetic Markers
keywords: Atherosclerosis; Carotid intima-media thickness; Plaque; Single-nucleotide polymorphisms