Genes associated with cancer, schizophrenia and type 2 diabetes in the circassian and Chechen populations in Jordan (original) (raw)
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Single-nucleotide polymorphisms as important risk factors of diabetes among Middle East population
Human Genomics
Diabetes is a chronic metabolic disorder that leads to the dysfunction of various tissues and organs, including eyes, kidneys, and cardiovascular system. According to the World Health Organization, diabetes prevalence is 8.8% globally among whom about 90% of cases are type 2 diabetes. There are not any significant clinical manifestations in the primary stages of diabetes. Therefore, screening can be an efficient way to reduce the diabetic complications. Over the recent decades, the prevalence of diabetes has increased alarmingly among the Middle East population, which has imposed exorbitant costs on the health care system in this region. Given that the genetic changes are among the important risk factors associated with predisposing people to diabetes, we examined the role of single-nucleotide polymorphisms (SNPs) in the pathogenesis of diabetes among Middle East population. In the present review, we assessed the molecular pathology of diabetes in the Middle East population that pav...
Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations
PeerJ, 2017
The prevalence of Type II Diabetes (T2D) has been increasing and has become a disease of significant public health burden in Jordan. None of the previous genome-wide association studies (GWAS) have specifically investigated the Middle East populations. The Circassian and Chechen communities in Jordan represent unique populations that are genetically distinct from the Arab population and other populations in the Caucasus. Prevalence of T2D is very high in both the Circassian and Chechen communities in Jordan despite low obesity prevalence. We conducted GWAS on T2D in these two populations and further performed meta-analysis of the results. We identified a novel T2D locus at chr20p12.2 at genome-wide significance (rs6134031, P = 1.12 × 10(-8)) and we replicated the results in the Wellcome Trust Case Control Consortium (WTCCC) dataset. Another locus at chr12q24.31 is associated with T2D at suggestive significance level (top SNP rs4758690, P = 4.20 × 10(-5)) and it is a robust eQTL for ...
Evidence for genetic contribution to the increased risk of type 2 diabetes in schizophrenia
Translational Psychiatry
The epidemiologic link between schizophrenia (SCZ) and type 2 diabetes (T2D) remains poorly understood. Here, we investigate the presence and extent of a shared genetic background between SCZ and T2D using genome-wide approaches. We performed a genome-wide association study (GWAS) and polygenic risk score analysis in a Greek sample collection (GOMAP) comprising three patient groups: SCZ only (n = 924), T2D only (n = 822), comorbid SCZ and T2D (n = 505); samples from two separate Greek cohorts were used as population-based controls (n = 1,125). We used genome-wide summary statistics from two large-scale GWAS of SCZ and T2D from the PGC and DIAGRAM consortia, respectively, to perform genetic overlap analyses, including a regional colocalisation test. We show for the first time that patients with comorbid SCZ and T2D have a higher genetic predisposition to both disorders compared to controls. We identify five genomic regions with evidence of colocalising SCZ and T2D signals, three of which contain known loci for both diseases. We also observe a significant excess of shared association signals between SCZ and T2D at nine out of ten investigated p value thresholds. Finally, we identify 29 genes associated with both T2D and SCZ, several of which have been implicated in biological processes relevant to these disorders. Together our results demonstrate that the observed comorbidity between SCZ and T2D is at least in part due to shared genetic mechanisms.
2018
Background: Type 2 Diabetes (T2D) is a multifactorial disease that encompasses environmental risk factors and the contribution of multiple genomic variants. Studies on the genetic components of T2D revealed many T2D-associated genetic polymorphisms in various populations. Lack of studies on the relation between gene polymorphism and T2D in Palestinians prompted us to examine the association between 16 known single nucleotide polymorphisms (SNPs) and T2D in this unexplored population. Method: In this case-control study, 100 T2D male patients and 100 control men were examined. The two groups were genotyped for the 16 genes polymorphisms using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Body Mass Index (BMI), and essential clinical parameters were measured for all the study participants. The relation between the 16 SNPs and T2D were statistically analyzed using appropriate tests. Results: Significant association was evident between IGF2BP and T2D, followed by CDKN2A/B (rs10811661) (OR=2.35, P-value=0.003), COL8A1 (rs792837) (OR=2.03, P-value=0.015), KCNQ1 (rs2237892) (OR=0.184, P-value=0.017), and KCNJ11 (rs5219; E23K) (OR=1.81, P-value=0.04), based on Armitage trend test. Among the 16 tested polymorphisms, a highly statistically significant association was evident between IGF2BP2 (rs4402960) and T2D [Odds ratio (OR)=3.28, P-value=7.46x10-8]. Conclusion: IGF2BP, CDKN2A/B, COL8A1, KCNQ1, and KCNJ11 gene variants are associated with T2D in the investigated population. This preliminary study sheds some light on the genetic components of T2D in Palestine.
Gene, 2020
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Genetics of type 2 diabetes in Arabs: What we know to date
International Journal of Diabetes Mellitus, 2009
Type 2 diabetes (T2D) is among the most challenging health issues of the 21st century and is associated with an alarming rise in the incidence. The Arab population is no exception to this trend. The pathophysiological processes that lead to development of T2D are still unclear, however impairment in insulin secretion and/or action is clearly indicated. T2D is a complex disease with susceptibility being governed by the interaction of multiple genetic and environmental effects. Previous studies indicated that variants in genes encoding the pancreatic b-cell K+ATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) are associated with type 2 diabetes. The common Pro12Ala polymorphism in peroxisome proliferator-activated receptor-c gene (PPAR-c) was confirmed in several studies to be associated with type 2 diabetes as well. More recently, studies reported variants within a novel gene, TCF7L2, as a putative susceptibility gene for type 2 diabetes across many ethnic backgrounds around the world. However, studies to date in Arab cohorts remain limited.
Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 2019
Background: Type 2 diabetes (T2D) is a polygenic and multi-factorial complex disease, the challenge to find genetic markers that could explain the risk of development of this disease still remains unresolved. The Arab region is one among the populations with a high prevalence of T2D and a large number of studies have been carried out in exploring the genetic factors associated with T2D risk. Aim: To summarize the recent developments in the Arab world based on the recent studies that had looked into genetic factors associated with the development of T2D in the Arab populations. Methods: A systematic literature search was conducted to identify studies published between 2015 and 2018 reporting genetic factors or polymorphisms associated with the risk of T2D in the Arab world. The online databases PubMed and Web of Science were used to perform the literature search. Conclusion: The present study has evaluated 14 studies published during the
Clinical Endocrinology, 2014
Background Previous genome-wide association studies have identified multiple type 2 diabetes (T2D) genetic risk loci in many populations. However, the contribution of these loci to T2D in the Middle Eastern populations with high T2D prevalence is unknown. Methods Here, we investigated the association of 38 T2D risk loci in the Saudi Arabian population (1166 patients with T2D and 1235 healthy controls), which has one of the world's highest prevalence of T2D. Results Eight common genetic variants showed a significant association with T2D in our study population. The effect sizes of these loci were comparable to those previously identified in other populations with the exception of HNF4A, which showed a trend for larger effect size in our study population (OR = 1Á27) compared to that reported in South Asian populations (OR = 1Á09; I 2 = 65Á9). Analysis of risk allele scores (RASs) defined by the 8 loci showed that subjects in the top RAS quintile (n = 480) had 2Á5-fold increase in disease risk compared to those in the bottom quintile (n = 480; P = 9Á5 9 10 À12 ). RASs were also associated with fasting glucose level (b = 0Á12; P = 2Á2 9 10 À9 ), but not with BMI (P = 0Á19). Analysis of a subgroup of subjects with BMI 30 resulted in two additional loci (SLC30A8; P = 0Á03, HMG20A; P = 0Á02) showing significant association with T2D. Conclusions We have shown for the first time that variants at WFS1, JAZF1, SLC30A8, CDKN2A/B, TCF7L2, KCNQ1, HMG20A, HNF4A and DUSP9 are associated with T2D in the Saudi population. Our findings also suggest substantial overlap of T2D risk loci across many ethnic groups regardless of disease prevalence.