title: Exome-Wide Association Analysis of Coronary Artery Disease in the Kingdom of Saudi Arabia Population.
abstract: Coronary Artery Disease (CAD) remains the leading cause of mortality worldwide. Mortality rates associated with CAD have shown an exceptional increase particularly in fast developing economies like the Kingdom of Saudi Arabia (KSA). Over the past twenty years, CAD has become the leading cause of death in KSA and has reached epidemic proportions. This rise is undoubtedly caused by fast urbanization that is associated with a life-style that promotes CAD. However, the question remains whether genetics play a significant role and whether genetic susceptibility is increased in KSA compared to the well-studied Western European populations. Therefore, we performed an Exome-wide association study (EWAS) in 832 patients and 1,076 controls of Saudi Arabian origin to test whether population specific, strong genetic risk factors for CAD exist, or whether the polygenic risk score for known genetic risk factors for CAD, lipids, and Type 2 Diabetes show evidence for an enriched genetic burden. Our results do not show significant associations for a single genetic locus. However, the heritability estimate for CAD for this population was high (h(2) = 0.53, S.E. = 0.1, p = 4e(-12)) and we observed a significant association of the polygenic risk score for CAD that demonstrates that the population of KSA, at least in part, shares the genetic risk associated to CAD in Western populations.
authors: Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Carolien G
authors: CG
authors: de Kovel
authors: Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Flip
authors: F
authors: Mulder
authors: Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Jessica
authors: J
authors: van Setten
authors: Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Ruben
authors: R
authors: van 't Slot
authors: Department of Medicine, King Fahd Hospital of the University, University of Dammam, Dammam, Kingdom of Saudi Arabia.
authors: Abdullah
authors: A
authors: Al-Rubaish
authors: Department of Medicine, King Fahd Hospital of the University, University of Dammam, Dammam, Kingdom of Saudi Arabia.
authors: Abdullah M
authors: AM
authors: Alshehri
authors: Department of Cardiology, King Fahd Military Medical Complex, Al-Khobar, Kingdom of Saudi Arabia.
authors: Khalid
authors: K
authors: Al Faraidy
authors: Prince Sultan Cardiac Center, Al-Ahssa, Kingdom of Saudi Arabia.
authors: Abdullah
authors: A
authors: Al-Ali
authors: King Fahd Hospital of the University, University of Dammam, Dammam, Kingdom of Saudi Arabia.
authors: Mohammed
authors: M
authors: Al-Madan
authors: Department of Medicine, Qatif Central Hospital, Qatif, Kingdom of Saudi Arabia.
authors: Issa
authors: I
authors: Al Aqaili
authors: Department of Medicine, King Fahd Hospital of the University, University of Dammam, Dammam, Kingdom of Saudi Arabia.
authors: Emmanuel
authors: E
authors: Larbi
authors: Department of Medicine, King Fahd Hospital of the University, University of Dammam, Dammam, Kingdom of Saudi Arabia.
authors: Rudaynah
authors: R
authors: Al-Ali
authors: College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors: Alhusain
authors: A
authors: Alzahrani
authors: Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Folkert W
authors: FW
authors: Asselbergs
authors: Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Bobby P C
authors: BP
authors: Koeleman
authors: Prince Mohammed Center for Research & Consultation Studies, College of Medicine, University of Dammam, Dammam, Kingdom of Saudi Arabia.
authors: Amein
authors: A
authors: Al-Ali
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D059472:Exome; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D012307:Risk Factors; D012529:Saudi Arabia / Q000453:epidemiology; D055815:Young Adult