Dataset Information

Replication of Type 2 diabetes-associated variants in a Saudi Arabian population.

ABSTRACT: Over 120 Type 2 diabetes (T2D) loci have been identified from genome-wide association studies (GWAS), mainly from Caucasian populations. Very limited knowledge is available on the Saudi Arabian population. In this study, 122 previously reported T2D-related variants from 84 loci were examined in a Saudi Arabian cohort of 1,578 individuals (659 T2D cases and 919 controls). Eleven single nucleotide polymorphisms (SNPs) corresponding to nine independent loci had a P value <0.05. If a more stringent Bonferroni threshold of P = 4.1?×?10-4 (?=?0.05/122) were applied, none of the SNPs would have reached the significance level. Nine of the SNPs with a P value <0.05 showed similar odds ratios as previously described, but rs11605924 ( CRY2) and rs9470794 ( ZFAND3) were in the opposite direction. This study demonstrates the importance of large-scale GWAS in the Saudi Arabian population to identify ethnicity-specific disease-associated variants.

SUBMITTER: Li-Gao R

PROVIDER: S-EPMC5966803 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Replication of Type 2 diabetes-associated variants in a Saudi Arabian population.

Li-Gao Ruifang R Wakil Salma M SM Meyer Brian F BF Dzimiri Nduna N Mook-Kanamori Dennis O DO

Physiological genomics 20180216 4

Over 120 Type 2 diabetes (T2D) loci have been identified from genome-wide association studies (GWAS), mainly from Caucasian populations. Very limited knowledge is available on the Saudi Arabian population. In this study, 122 previously reported T2D-related variants from 84 loci were examined in a Saudi Arabian cohort of 1,578 individuals (659 T2D cases and 919 controls). Eleven single nucleotide polymorphisms (SNPs) corresponding to nine independent loci had a P value <0.05. If a more stringent ...[more]

PMID: 29451423

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Project description:BackgroundKeratoconus (KC) is the most common primary ectatic disease of the cornea and a major indication for corneal transplant. To date, limited KC-associated-risk loci have been identified. Association has recently been suggested between KC and 8 single nucleotide polymorphisms (SNPs) in the genomic regions of FNDC3B, COL4A3, MPDZ-NF1B, RXRA-COL5A1, LCN12-PTGDS, FOXO1, and BANP-ZNF469. These SNPs are associated with central corneal thickness (CCT), a known risk factor to KC. We are questioning whether these SNPs are significantly associated with KC in a Saudi Arabian population. The study included 108 unrelated KC cases and 300 controls. Patients were diagnosed with KC according to the Schimpff-flow based elevation map of the cornea. DNA genotyping was done using probe-based allelic discrimination TaqMan assays. Allele frequencies were compared between the cases and controls.ResultsAll SNPs were successfully genotyped with high efficiency (>95 %). The SNPs had no significant deviation in cases or controls from Hardy-Weinberg Equilibrium (HWE, p value > 0.05). None of the selected SNPs were significantly associated with KC in the Saudi Arabian population. However, we replicated the same trend of minor allele frequency (MAF) between cases and controls reported by a recent GWAS regarding the 5 SNPs rs4894535 (FNDC3B, chr3: 171995605), rs1536482 (RXRA-COL5A1, chr9: 137440528), rs7044529 (COL5A1, chr9: 137568051), rs11145951 (LCN12-PTGDS, chr9: 139860264), and rs2721051 (FOXO1, chr13: 41110884).ConclusionsThis is the first study investigating the association of these SNPs with KC in a population from Saudi Arabia. We replicated the same trend of MAF alteration of the association between the SNPs rs4894535 (FNDC3B, chr3: 171995605), rs7044529 (COL5A1, chr9: 137568051), rs11145951 (LCN12-PTGDS, chr9: 139860264) and rs2721051 (FOXO1, chr13: 41110884) and KC-risk as reported by a recently published GWAS. Consistently replicated population-based studies are necessary to identify and/or confirm genetic susceptibility for certain diseases. We acknowledge that the lack of significance in our study is due to our small sample size and insufficient statistical power; however our data still add to the body of evidence of potential KC-candidate SNPs. This report aims at supporting the possible association between CCT-associated SNPs and KC susceptibility.

Project description:BACKGROUND:Type 2 diabetes mellitus (T2DM) is a chronic and multifactorial disease with a rapidly rising incidence in Saudi Arabia. Various genes including zinc finger protein 1 (JAZF1) and tetraspanin 8/leucine-rich repeat-containing G protein-coupled receptor (TSPAN8/LGR5) have been previously described to be associated with T2DM. This study investigated the association of JAZF1 (rs864745) and TSPAN8 (rs7961581) with T2DM in a Saudi population. METHODS:Genomic DNA samples from 400 Saudi T2DM patients and 400 healthy controls were genotyped and analyzed using a polymerase chain reaction-restriction fragment length polymorphism method. The difference between the genotype frequencies were carried out with Chi-square test. Odds ratio, 95 % confidence intervals and p values were calculated using multinomial logistic regression. Dominant and recessive models were implemented to show the statistical significances. Analysis of variance was used to compare differences between genotypes for the various parameters. RESULTS:Distribution frequencies of the AA, AG, and GG genotypes of JAZF1 (rs864745) differed significantly among T2DM patients and healthy controls (p < 0.05). The AG and GG genotypes were independently and significantly associated with a T2DM risk after adjusting for factors such as age, sex, and body mass index [odds ratio (OR) 2.1 (95 % confidence interval (CI) 1.3-3.4); p = 0.002] and [OR 1.9 (95 % CI 1.2-3.1); p = 0.005], respectively. A genotype-based stratification of anthropometric and biochemical data revealed that the AG + GG genotype is associated with waist circumference (p = 0.04) and fasting blood glucose (p = 0.01) and high-density lipoprotein cholesterol levels (p = 0.02). None of the allele or genotype showed the significant association between the T2DM cases and control subjects in rs7961581 polymorphism in TSPAN8/LGR5 gene. CONCLUSION:The rs864745 variant in JAZF1 gene may act as genetic risk factors for the development of T2DM in a Saudi population.

Dataset Information

Replication of Type 2 diabetes-associated variants in a Saudi Arabian population.

Publications

Replication of Type 2 diabetes-associated variants in a Saudi Arabian population.

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