Genome-wide association study identifies novel risk variants from RPS6KA1, CADPS, VARS, and DHX58 for fasting plasma glucose in Arab population

• Published in: Scientific reports 2020-01, Vol.10 (1), p.152-152, Article 152
• Main Authors: Hebbar, Prashantha, Abu-Farha, Mohamed, Alkayal, Fadi, Nizam, Rasheeba, Elkum, Naser, Melhem, Motasem, John, Sumi Elsa, Channanath, Arshad, Abubaker, Jehad, Bennakhi, Abdullah, Al-Ozairi, Ebaa, Tuomilehto, Jaakko, Pitkaniemi, Janne, Alsmadi, Osama, Al-Mulla, Fahd, Thanaraj, Thangavel Alphonse
• Format: Article
• Language: English
• Subjects: 45; 45/43; 631/208/205/2138; 631/208/721; Arabs - genetics; Biomarkers - analysis; Blood Glucose - analysis; Calcium-Binding Proteins - genetics; Case-Control Studies; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - pathology; Etiology; Fasting; Female; Gene Expression Profiling; Gene Expression Regulation; Genetic Predisposition to Disease; Genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotype; Genotypes; Genotyping; Hemoglobin; Humanities and Social Sciences; Humans; Insulin; Insulin Resistance; Kuwait - epidemiology; Male; multidisciplinary; Phenotype; Polymorphism, Single Nucleotide; Prognosis; Replication; Ribosomal Protein S6 Kinases, 90-kDa - genetics; RNA Helicases - genetics; Science; Science (multidisciplinary); Statistical analysis; Triglycerides; Valine-tRNA Ligase - genetics; Vesicular Transport Proteins - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-57072-9

Consanguineous populations of the Arabian Peninsula, which has seen an uncontrolled rise in type 2 diabetes incidence, are underrepresented in global studies on diabetes genetics. We performed a genome-wide association study on the quantitative trait of fasting plasma glucose (FPG) in unrelated Arab individuals from Kuwait (discovery-cohort:n = 1,353; replication-cohort:n = 1,196). Genome-wide genotyping in discovery phase was performed for 632,375 markers from Illumina HumanOmniExpress Beadchip; and top-associating markers were replicated using candidate genotyping. Genetic models based on additive and recessive transmission modes were used in statistical tests for associations in discovery phase, replication phase, and meta-analysis that combines data from both the phases. A genome-wide significant association with high FPG was found at rs1002487 ( RPS6KA1 ) (p-discovery = 1.64E-08, p-replication = 3.71E-04, p-combined = 5.72E-11; β-discovery = 8.315; β-replication = 3.442; β-combined = 6.551). Further, three suggestive associations (p-values