title: A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs.
abstract: BACKGROUND
  Multiple loci have been identified for coronary artery disease (CAD) by genome-wide association studies (GWAS), but no such studies on CAD incidence has been reported yet for any Middle Eastern population.
  
  
  METHODS
  In this study, we performed a GWAS for CAD and myocardial infarction (MI) incidence in 5668 Saudis of Arab descent using the Affymetrix Axiom Genotyping platform.
  
  
  RESULTS
  We describe SNPs at 16 loci that showed significant (P < 5 × 10(-8)) or suggestive GWAS association (P < 1 × 10(-5)) with CAD or MI, in the ethnic Saudi Arab population. Among the four variants reaching GWAS significance in the present study, the rs10738607_G [0.78(0.71-0.85); p = 2.17E-08] in CDNK2A/B gene was associated with CAD. Two other SNPs on the same gene, rs10757274_G [0.79(0.73-0.86); p = 2.98E-08] and rs1333045_C [0.79(0.73-0.86); p = 1.15E-08] as well as the rs9982601_T [1.38(1.23-1.55); p = 3.49E-08] on KCNE2 were associated with MI. These variants have been previously described in other populations. Several SNPs, including the rs7421388 (PLCL1) and rs12541758 (TRPA1) displaying a suggestive GWAS association (P < 1 × 10(-5)) with CAD as well as rs41411047 (RNF13), rs32793 (PDZD2) and rs4739066 (YTHDF3), similarly showing weak association with MI, were confirmed in an independent dataset. Furthermore, our estimation of heritability of CAD and MI based on observed genome-wide sharing in unrelated Saudi Arabs was approximately 33% and 44%, respectively.
  
  
  CONCLUSIONS
  Our study has identified susceptibility variants for CAD/MI in ethnic Arabs. These findings provide further insights into pathways contributing to the susceptibility for CAD and will enable more comprehensive genetic studies of these diseases in Middle East populations.
authors.affiliation: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Salma M
authors.initials: SM
authors.lastname: Wakil
authors.affiliation: Harry Perkins Institute of Medical Research, University of Western Australia, Australia.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Ram
authors.affiliation: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Nzioka P
authors.initials: NP
authors.lastname: Muiya
authors.affiliation: Harry Perkins Institute of Medical Research, University of Western Australia, Australia.
authors.forename: Munish
authors.initials: M
authors.lastname: Mehta
authors.affiliation: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Editha
authors.initials: E
authors.lastname: Andres
authors.affiliation: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Nejat
authors.initials: N
authors.lastname: Mazhar
authors.affiliation: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Batoul
authors.initials: B
authors.lastname: Baz
authors.affiliation: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Samya
authors.initials: S
authors.lastname: Hagos
authors.affiliation: King Faisal Heart Institute, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Maie
authors.initials: M
authors.lastname: Alshahid
authors.affiliation: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Brian F
authors.initials: BF
authors.lastname: Meyer
authors.affiliation: Harry Perkins Institute of Medical Research, University of Western Australia, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: Morahan
authors.affiliation: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Electronic address: dzimiri@kfshrc.edu.sa.
authors.forename: Nduna
authors.initials: N
authors.lastname: Dzimiri
mesh_terms: D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D012529:Saudi Arabia / Q000453:epidemiology
keywords: CDKN2A/B; CXCL12; Coronary artery disease; Genome-wide association; Haplotypes; Heritability; KCNE2; Myocardial infarction