A5012302225- Genetic Associations and Epidemiology
- Pancreatic function and diabetes
- Diabetes and associated disorders
- COVID-19 Clinical Research Studies
- Epigenetics and DNA Methylation
- SARS-CoV-2 and COVID-19 Research
- Genomics and Rare Diseases
- RNA modifications and cancer
- Forensic and Genetic Research
- Adipose Tissue and Metabolism
- Liver Disease Diagnosis and Treatment
- Regulation of Appetite and Obesity
- Mitochondrial Function and Pathology
- Diet and metabolism studies
- Nutrition, Genetics, and Disease
- Hemoglobinopathies and Related Disorders
- Metabolomics and Mass Spectrometry Studies
- Metabolism and Genetic Disorders
- Diabetes Treatment and Management
- Immune responses and vaccinations
- Pharmacogenetics and Drug Metabolism
- Renal and related cancers
- Computational Drug Discovery Methods
- Receptor Mechanisms and Signaling
- Genetic and Kidney Cyst Diseases
Dasman Diabetes Institute
2015-2025
COVID-19 is challenging healthcare preparedness, world economies, and livelihoods. The infection death rates associated with this pandemic are strikingly variable in different countries. To elucidate discrepancy, we analyzed 2431 early spread SARS-CoV-2 sequences from GISAID. We estimated continental-wise admixture proportions, assessed haplotype block estimation, tested for the presence or absence of strains' recombination. Herein, identified 1010 unique missense mutations seven clusters....
The severity of the new COVID-19 pandemic caused by SARS-CoV-2 virus is strikingly variable in different global populations. uses ACE2 as a cell receptor, TMPRSS2 protease, and FURIN peptidase to invade human cells. Here, we investigated 1,378 whole-exome sequences individuals from Middle Eastern populations (Kuwait, Qatar, Iran) explore natural variations ACE2, TMPRSS2, genes. We identified two activating variants (K26R N720D) gene that are more common Europeans than Eastern, East Asian,...
Objectives: Type 2 diabetes (T2D) is a metabolic disease of major public health concern. It impacts peripheral tissues and the central nervous system, leading to systemic dysmetabolism neurocognitive impairments, including memory deficits, anxiety, depression. The determinants these impairments remain unidentified. Here, we sought address this question by developing proprietary (P-) high-fat diet (HFD), in which glucose intolerance precedes weight gain insulin resistance. Methods: P-HFD...
Multisystem inflammatory syndrome in children (MIS-C) is a severe complication arising from SARS-CoV-2 infection, with indications that rare inborn errors of immunity may play role its pathogenesis. Recent studies suggest genetic predispositions, particularly monogenic forms, could significantly influence the immune responses to MIS-C. We analysed 24 under 12 years old, all whom met criteria provided by World Health Organization, 2020 for MIS-C diagnosis, Paediatric COVID-19 Registry Kuwait...
The State of Kuwait is characterized by settlers from Saudi Arabia, Iran, and other regions the Arabian Peninsula. settlements subsequent admixtures have shaped genetics Kuwait. High prevalence recessive disorders metabolic syndromes (that increase risk diabetes) seen in peninsula. Understanding genetic structure its population will aid studies designed to decipher underlying causes these disorders. In this study, we analyzed 572,366 SNP markers 273 Kuwaiti natives genotyped using illumina...
Population of the State Kuwait is composed three genetic subgroups inferred Persian, Saudi Arabian tribe and Bedouin ancestry. The subgroup traces its origin to Najd region Arabia. By sequencing two whole genomes thirteen exomes from this at high coverage (>40X), we identify 4,950,724 Single Nucleotide Polymorphisms (SNPs), 515,802 indels 39,762 structural variations. Of identified variants, 10,098 (8.3%) exomic SNPs, 139,923 (2.9%) non-exomic 5,256 (54.3%) indels, 374,959 (74.08%) are...
The 1000 Genome project paved the way for sequencing diverse human populations. New genome projects are being established to sequence underrepresented populations helping in understanding genetic diversity. Kuwait Project an initiative individual genomes from three subgroups of Kuwaiti population namely, Saudi Arabian tribe; "tent-dwelling" Bedouin; and Persian, attributing their ancestry different regions Peninsula modern-day Iran (West Asia). These were line with settlement history...
To characterize the underlying genetic and molecular defects in a consanguineous family with lifelong blood disorder manifested thrombocytopenia (low platelets count) anemia.Genetic linkage analysis, exome sequencing, functional genomics were carried out to identify defective gene.We identified novel truncation mutation (p.C108*) chromosome 6 open reading frame 25 (C6orf25) gene this family. We also showed p.C108* was responsible for destabilizing encoded truncated G6B protein. Unlike form,...
Despite a high prevalence of metabolic trait related diseases in Arabian Peninsula, there is lack convincingly identified genetic determinants for traits this population. Arab populations are underrepresented global genome-wide association studies. We genotyped 1965 unrelated individuals from Kuwait using Cardio-MetaboChip, and tested SNP associations with 13 traits. Models based on recessive mode inheritance Chr15:40531386-rs12440118/ZNF106/W->R as risk variant associated...
Abstract Consanguineous populations of the Arabian Peninsula have been underrepresented in global efforts that catalogue human exome variability. We sequenced 291 whole exomes unrelated, healthy native Arab individuals from Kuwait to a median coverage 45X and characterised 170,508 single-nucleotide variants (SNVs), which 21.7% were ‘personal’. Up 12% SNVs novel 36% population-specific. Half rare 54% missense variants. The study complemented Greater Middle East Variome by way reporting many...
Kuwaiti native population comprises three distinct genetic subgroups of Persian, "city-dwelling" Saudi Arabian tribe, and nomadic "tent-dwelling" Bedouin ancestry. subgroup is characterized by presence 17% African ancestry; it owes origin to tribes the deserts Peninsula North Africa. By sequencing whole genome a male from this at 41X coverage, we report 3,752,878 SNPs, 411,839 indels, 8451 structural variations. Neighbor-joining tree, based on shared variant positions carrying disease-risk...
Abnormal blood lipid levels are influenced by genetic and lifestyle/dietary factors. Although many variants associated with traits have been identified in Europeans, similar data Middle Eastern populations limited. We performed a genome-wide association study Arab individuals (discovery cohort: 1,353; replication 1,176) from Kuwait to identify possible associations of high levels. used Illumina HumanOmniExpress BeadChip candidate SNP genotyping the discovery phases, respectively. For tests,...
Abstract Genetic variants responsible for Maturity-Onset-Diabetes of the Young (MODY) in Kuwait were investigated. A newly established a National Referral Clinic, Dasman Diabetes Institute (DDI-NRC), assessed forty-five members from 31 suspected MODY families by whole exome sequencing. Thirty-three 45 samples independently sequenced at DDI-NRI, Exeter University, UK ( https://www.diabetesgenes.org/ ) using targeted 21-gene panel approach. Pathogenic mutations GCK, HNF1A, HNF1B, HNF4A, and...
Background The Kuwaiti and Qatari populations have a high prevalence of obesity, major risk factor for various metabolic disorders. Previous studies independently explored mitochondrial DNA (mtDNA) variations their association with obesity in these populations. This study aims to investigate the role mtDNA haplogroups variants among Gulf Methods Whole exome sequencing data from 1,112 participants (348 Kuwaitis 764 Qataris) were analyzed variants. Participants classified as obese or non-obese...
Abstract The severity of the new COVID-19 pandemic caused by SARS-CoV-2 virus is strikingly variable in different global populations. uses ACE2 as a cell receptor, TMPRSS2 protease, and FURIN peptidase to invade human cells. Here, we investigated 1,378 whole-exome sequences individuals from Middle Eastern populations (Kuwait, Qatar, Iran) explore natural variations , TMPRSS2, genes. We identified two activating variants (K26R N720D) gene that are more common Europeans than Eastern, East...
Abstract Consanguineous populations of the Arabian Peninsula, which has seen an uncontrolled rise in type 2 diabetes incidence, are underrepresented global studies on genetics. We performed a genome-wide association study quantitative trait fasting plasma glucose (FPG) unrelated Arab individuals from Kuwait (discovery-cohort:n = 1,353; replication-cohort:n 1,196). Genome-wide genotyping discovery phase was for 632,375 markers Illumina HumanOmniExpress Beadchip; and top-associating were...
Abstract There has recently been a growing interest in examining the role of epigenetic modifications, such as DNA methylation, etiology type 1 diabetes (T1D). This study aimed to delineate differences methylation patterns between T1D-affected and healthy individuals by genome-wide from three Arab families Kuwait with mono-/dizygotic twins non-twinned siblings. Bisulfite sequencing peripheral blood affected each was performed. Methylation profiles were compared those Principal component...
Abstract While the Arabian population has a high prevalence of metabolic disorders, it not been included in global studies that identify genetic risk loci for traits. Determining transferability such largely Euro-centric established is essential to transfer research tools/resources, and drug targets generated by broad range ethnic populations. Further, consideration populations as Arabs, are characterized consanguinity level inbreeding, can lead identification novel loci. We imputed...
Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal monogenic disease, characterized by bilateral accumulation of fluid-filled cysts leading to progressive volume enlargement and gradual impairment function, often resulting in end-stage disease. Kuwait could provide valuable genetic insights about ADPKD, including intrafamilial phenotypic variation, given its large household size. This study aims a comprehensive description pathogenic variants linked ADPKD Kuwaiti...
Recent research illustrates the role of central melanocortin signaling and leptin in regulation arterial blood pressure animal models. Unraveling genetic basis interactions between humans will provide new insight into pressure.Our study population consisted 332 Kuwaiti natives. Polymorphisms from exons leptin, MC3R, MC4R genes were identified by Sanger sequencing. MC3R expression levels determined. Linear regression models, adjusted for age, gender, antihypertensive medication, body mass...
Objective Despite alarming obesity levels in the Arabian Peninsula, its population lacks convincingly identified genetic determinants of obesity. A genome‐wide association study was performed for obesity‐related anthropometric traits Arabs and to decipher mechanisms by which variants mediate traits. Methods The Illumina HumanOmniExpress BeadChip used genotype 1,353 Arab individuals (largely with Class I obesity) from Kuwait. Genome‐wide tests were performed. Top associations tested...
Type 1 diabetes (T1D) is characterized by the progressive destruction of pancreatic β-cells, leading to insulin deficiency and lifelong dependency on exogenous insulin. Higher estimates heritability rates in monozygotic twins, followed dizygotic twins sib-pairs, indicate role genetics pathogenesis T1D. The incidence prevalence T1D are alarmingly high Kuwait. Consanguineous marriages account for 50-70% all Kuwait, an excessive burden recessive allele enrichment clustering familial disorders....
Background/Objectives Whole-exome sequencing is a valuable tool to determine genetic variations that are associated with rare and common health conditions. A limited number of studies demonstrated mitochondrial DNA can be captured using whole-exome sequencing. Previous have suggested variants haplogroup lineages obesity. Therefore, we investigated the role haplogroups contributing risk obesity in Arabs Kuwait exome data. Subjects/Methods Indirect genomes were extracted from data 288...
With the tremendous advancements in genome sequencing technology field of pharmacogenomics, data have to be made accessible more efficiently utilized by broader clinical disciplines. Physicians who require drug–genome interactome information, been challenged complicated pharmacogenomic star-based classification system. We present here an end-to-end web-based pharmacogenomics tool, PharmaKU, which has a comprehensive easy-to-use interface. PharmaKU can help overcome several hurdles posed...