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 (h2 = 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.
Highlights
Coronary Artery Disease (CAD) is the major cause of death in most countries and has been reported to be responsible for 32% of deaths in Western populations [1]
The samples were genotyped using the Illumina Infinium HumanExome BeadChip v1.1. This chip provides focused coverage for putative functional exonic variants and common Single Nucleotide Polymorphisms (SNPs) that are previously associated to CAD, metabolic syndrome and Type 2 Diabetes (T2D)
We conclude that our study suggests that of the known CAD risk loci, none confer higher risk to the Kingdom of Saudi Arabia (KSA) population and these can not explain the high prevalence of CAD in the KSA population
Summary
The written informed consent forms have all been documented electronically against each participants name and data. The ethics doi:10.1371/journal.pone.0146502.g004 committee approved the project and the consent procedure. All patients and controls were randomly selected from five major hospitals in the Eastern Province of KSA, where the patient groups are derived from the 13 provinces of the Kingdom. In total 866 CAD patients (321 female, 531 male, 14 gender unknown) and 1,150 control individuals (235 female, 847 male, 68 gender unknown) were collected for genotyping. The majority of patient cases had experienced a myocardial event (98%) and 672 (78%) had diabetes. The majority of patient cases were overweight as defined by a BMI above 25 (520, 77%), and 292 (43%) were obese (BMI greater than 30) (Fig 4)
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