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

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Hebbar , P , Abu-Farha , M , Alkayal , F , Nizam , R , Elkum , N , Melhem , M , John , S E , Channanath , A , Abubaker , J , Bennakhi , A , Al-Ozairi , E , Tuomilehto , J , Pitkäniemi , J , Alsmadi , O , Al-Mulla , F & Thanaraj , T A 2020 , ' Genome-wide association study identifies novel risk variants from RPS6KA1, CADPS, VARS, and DHX58 for fasting plasma glucose in Arab population ' , Scientific Reports , vol. 10 , no. 1 , 152 . https://doi.org/10.1038/s41598-019-57072-9

Title: Genome-wide association study identifies novel risk variants from RPS6KA1, CADPS, VARS, and DHX58 for fasting plasma glucose in Arab population
Author: 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; Pitkäniemi, Janne; Alsmadi, Osama; Al-Mulla, Fahd; Thanaraj, Thangavel Alphonse
Contributor: University of Helsinki, Faculty of Medicine
University of Helsinki, Clinicum
University of Helsinki, Clinicum
Date: 2020-01-13
Language: eng
Number of pages: 17
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/313231
Abstract: 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; beta-discovery = 8.315; beta-replication = 3.442; beta-combined = 6.551). Further, three suggestive associations (p-values <8.2E-06) with high FPG were observed at rs487321 (CADPS), rs707927 (VARS and 2Kb upstream of VWA7), and rs12600570 (DHX58); the first two markers reached genome-wide significance in the combined analysis (p-combined = 1.83E-12 and 3.07E-09, respectively). Significant interactions of diabetes traits (serum triglycerides, FPG, and glycated hemoglobin) with homeostatic model assessment of insulin resistance were identified for genotypes heterozygous or homozygous for the risk allele. Literature reports support the involvement of these gene loci in type 2 diabetes etiology.
Subject: GENETIC ARCHITECTURE
DIABETES-MELLITUS
TYPE-2
LOCI
HOMEOSTASIS
DISEASE
SUSCEPTIBILITY
HOMOZYGOSITY
AMERICANS
EFFICIENT
3142 Public health care science, environmental and occupational health
3111 Biomedicine
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