title: Association of a sequence variant in DAB2IP with coronary heart disease.
abstract: OBJECTIVE
  A sequence variant, rs7025486[A], in DAB2IP on chromosome 9q33 has recently been associated with coronary heart disease (CHD). We sought to replicate this finding and to investigate associations with a panel of inflammatory and haemostatic biomarkers. We also sought to examine whether this variant, in combination with a chromosome 9p21 CHD variant (rs10757278) and the Framingham risk score (FRS), could improve the prediction of events compared with the FRS alone.
  
  
  RESULTS
  rs7025486 was genotyped in 1386 CHD cases and 3532 controls and was associated with CHD [odds ratio (OR) of 1.16, 95% confidence interval (CI) 1.05-1.29, P= 0.003]. Meta-analysis, using data from the original report and from genome-wide association studies in both the Wellcome Trust Case Control Consortium and the Cardiovascular Health Study, comprising 9968 cases and 20 048 controls, confirmed the association (OR of 1.10, 95% CI 1.06-1.14, P= 3.2 × 10(-6)). There was no association with a panel of CHD biomarkers, including any lipid, inflammation, or coagulation trait, nor with telomere length. Addition to the FRS of this variant plus rs10757278 on chromosome 9p21 improved the area under the receiver-operating characteristic curve (A(ROC)) from 0.61 to 0.64 (P= 0.03) as well as improving the reclassification (net reclassification index = 11.1%, P= 0.007).
  
  
  CONCLUSIONS
  This study replicates a previous association of a variant in DAB2IP with CHD. Addition of multiple variants improves the performance of predictive models based upon classical cardiovascular risk factors.
authors: BHF Laboratories, Department of Medicine, Centre for Cardiovascular Genetics, University College London (UCL), The Rayne Building, 5 University Street, London WC1E 6JF, UK. seamus.harrison@ucl.ac.uk
authors: Seamus C
authors: SC
authors: Harrison
authors: Jackie A
authors: JA
authors: Cooper
authors: Kawah
authors: K
authors: Li
authors: Phillipa J
authors: PJ
authors: Talmud
authors: Reecha
authors: R
authors: Sofat
authors: Jeffery W
authors: JW
authors: Stephens
authors: Anders
authors: A
authors: Hamsten
authors: Julie
authors: J
authors: Sanders
authors: Hugh
authors: H
authors: Montgomery
authors: Andrew
authors: A
authors: Neil
authors: Steve E
authors: SE
authors: Humphries
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D020703:ras GTPase-Activating Proteins / Q000235:genetics*
chemical_list: C462952:DAB2IP protein, human; D020703:ras GTPase-Activating Proteins