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1.  Copy number variations in the genome of the Qatari population 
BMC Genomics  2015;16:834.
The populations of the Arabian Peninsula remain the least represented in public genetic databases, both in terms of single nucleotide variants and of larger genomic mutations. We present the first high-resolution copy number variation (CNV) map for a Gulf Arab population, using a hybrid approach that integrates array genotyping intensity data and next-generation sequencing reads to call CNVs in the Qatari population.
CNVs were detected in 97 unrelated Qatari individuals by running two calling algorithms on each of two primary datasets: high-resolution genotyping (Illumina Omni 2.5M) and high depth whole-genome sequencing (Illumina PE 100bp). The four call-sets were integrated to identify high confidence CNV regions, which were subsequently annotated for putative functional effect and compared to public databases of CNVs in other populations. The availability of genome sequence was leveraged to identify tagging SNPs in high LD with common deletions in this population, enabling their imputation from genotyping experiments in the future.
Genotyping intensities and genome sequencing data from 97 Qataris were analyzed with four different algorithms and integrated to discover 16,660 high confidence CNV regions (CNVRs) in the total population, affecting ~28 Mb in the median Qatari genome. Up to 40 % of all CNVs affected genes, including novel CNVs affecting Mendelian disease genes, segregating at different frequencies in the 3 major Qatari subpopulations, including those with Bedouin, Persian/South Asian, and African ancestry. Consistent with high consanguinity levels in the Bedouin subpopulation, we found an increased burden for homozygous deletions in this group. In comparison to known CNVs in the comprehensive Database of Genomic Variants, we found that 5 % of all CNVRs in Qataris were completely novel, with an enrichment of CNVs affecting several known chromosomal disorder loci and genes known to regulate sugar metabolism and type 2 diabetes in the Qatari cohort. Finally, we leveraged the availability of genome sequence to find suitable tagging SNPs for common deletions in this population.
We combine four independently generated datasets from 97 individuals to study CNVs for the first time at high-resolution in a Gulf Arab population.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1991-5) contains supplementary material, which is available to authorized users.
PMCID: PMC4618522  PMID: 26490036
Copy number variation; Next-generation sequencing; Genotyping; Genomics; Mendelian disease; Qatar
2.  Role of SLMAP genetic variants in susceptibility of diabetes and diabetic retinopathy in Qatari population 
Overexpression of SLMAP gene has been associated with diabetes and endothelial dysfunction of macro- and micro-blood vessels. In this study our primary objective is to explore the role of SLMAP gene polymorphisms in the susceptibility of type 2 diabetes (T2DM) with or without diabetic retinopathy (DR) in the Qatari population.
A total of 342 Qatari subjects (non-diabetic controls and T2DM patients with or without DR) were genotyped for SLMAP gene polymorphisms (rs17058639 C > T; rs1043045 C > T and rs1057719 A > G) using Taqman SNP genotyping assay.
SLMAP rs17058639 C > T polymorphism was associated with the presence of DR among Qataris with T2DM. One-way ANOVA and multiple logistic regression analysis showed SLMAP SNP rs17058639 C > T as an independent risk factor for DR development. SLMAP rs17058639 C > T polymorphism also had a predictive role for the severity of DR. Haplotype Crs17058639Trs1043045Ars1057719 was associated with the increased risk for DR among Qataris with T2DM.
The data suggests the potential role of SLMAP SNPs as a risk factor for the susceptibility of DR among T2DM patients in the Qatari population.
Electronic supplementary material
The online version of this article (doi:10.1186/s12967-015-0411-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4335364  PMID: 25880194
SLMAP; Endothelial dysfunction; Genetic susceptibility; Qatari population; Diabetic retinopathy; T2DM
3.  Prevalence of the ApoE Arg145Cys Dyslipidemia At-risk Polymorphism in African-derived Populations 
The American journal of cardiology  2013;113(2):302-308.
Apolipoprotein E (ApoE), a protein component of blood lipid particles, plays an important role in lipid transport. Different mutations in the ApoE gene have been associated with various clinical phenotypes. In an initiated study of Qataris, we observed that 17% of the African-derived genetic subgroup were heterozygotes for a rare Arg145Cys (R145C) variant that functions as a dominant trait with incomplete penetrance associated with type III hyperlipoproteinemia. Based on this observation, we hypothesized that the R145C polymorphism may be common in African-derived populations. The prevalence of the R145C variant was assessed worldwide in the 1000 Genomes Project (1000G) and in 1012 Caucasians and 1226 African-Americans in New York City. The 1000G data demonstrated that the R145C polymorphism is rare in non-African derived populations, but present in 5–12% of sub-Saharan African-derived populations. The R145C polymorphism was also rare in New York City Caucasians (1/1012, 0.1%), but strikingly, 53 (4.3%) of 1226 New York City African-Americans were R145C heterozygotes. Lipid profiles of the Qatari and New York R145C were compared to controls. Qatari R145C had higher triglyceride levels compared to Qatari controls (p<0.007) and NY African-Americans R145C had an average of 52% higher fasting triglyceride levels compared to NY African-American controls (p<0.002). Based on these observations, there are likely millions of people worldwide derived from Sub-Saharan Africans that are ApoE R145C. In conclusion, while larger epidemiologic studies are necessary to determine the long-term consequences of this polymorphism, the available evidence suggests it is a common cause of a mild triglyceride dyslipidemia.
PMCID: PMC3943837  PMID: 24239320
Apolipoprotein E; polymorphism; lipids; dyslipidemia; ethnicity
4.  Exome Sequencing Identifies Potential Risk Variants for Mendelian Disorders at High Prevalence in Qatar 
Human mutation  2013;35(1):105-116.
Exome sequencing of families of related individuals has been highly successful in identifying genetic polymorphisms responsible for Mendelian disorders. Here, we demonstrate the value of the reverse approach, where we use exome sequencing of a sample of unrelated individuals to analyze allele frequencies of known causal mutations for Mendelian diseases. We sequenced the exomes of 100 individuals representing the three major genetic subgroups of the Qatari population (Q1 Bedouin, Q2 Persian-South Asian, Q3 African) and identified 37 variants in 33 genes with effects on 36 clinically significant Mendelian diseases. These include variants not present in 1000 Genomes and variants at high frequency when compared to 1000 Genomes populations. Several of these Mendelian variants were only segregating in one Qatari subpopulation, where the observed subpopulation specificity trends were confirmed in an independent population of 386 Qataris. Pre-marital genetic screening in Qatar tests for only 4 out of the 37, such that this study provides a set of Mendelian disease variants with potential impact on the epidemiological profile of the population that could be incorporated into the testing program if further experimental and clinical characterization confirms high penetrance.
PMCID: PMC3908915  PMID: 24123366
Mendelian; consanguinity; exome sequencing; OMIM; diagnostic biomarkers
5.  Prevention of type II diabetes mellitus in Qatar: Who is at risk? 
Qatar Medical Journal  2014;2014(2):70-81.
Background: Type II diabetes mellitus (DM) is one of the leading chronic diseases in Qatar as well as worldwide. However, the risk factors for DM in Qatar and their prevalence are not well understood. We conducted a case-control study with the specific aim of estimating, based on data from outpatients with DM in Qatar (cases) and outpatient/inpatient controls, the association between demographic/lifestyle factors and DM. Methods: A total of 459 patients with DM from Hamad General Hospital (HGH) outpatient adult diabetes clinics, and 342 control patients from various outpatient clinics and inpatient departments within Hamad Medical Corporation (HMC) (years 2006–2008), were recruited. The association between risk factors and DM was evaluated using bivariate and multivariable logistic regression analyses. In addition to odds ratios (OR) and 95% confidence intervals (95% CI), we estimated the population attributable risk fractions for the DM demographic/lifestyle risk factors. Results: Qatari nationality was the strongest risk factor for DM (adjusted OR = 5.5; 95% CI = 3.5–8.6; p < 0.0001), followed by higher monthly income (defined as ≥ 3000 Qatari Riyals, adjusted OR = 5.1; 95% CI = 3.0–8.7; p < 0.0001), age >65 years (adjusted OR = 3.3; 95% CI = 0.9–11.4; p = 0.06), male gender (adjusted OR = 2.9; 95% CI = 1.8-4.8; p < 0.0001), obesity (BMI ≥ 30, adjusted OR = 2.2; 95% CI = 1.5-3.2; p < 0.0001), no college education (adjusted OR = 1.7; 95% CI = 1.2–2.6; p = 0.009), and no daily vigorous/moderate activity (adjusted OR = 1.5; 95% CI = 0.9–2.3; p = 0.12). Among Qatari nationals, obesity was found to be the main risk factor for DM (unadjusted OR = 3.0; 95% CI = 1.6–5.6; p < 0.0001), followed by no college education (unadjusted OR = 2.7; 95% CI = 1.5–5.1; p = 0.001), while consanguinity did not appear to play a major role in predicting DM (unadjusted OR = 1.5; 95% CI = 0.8–2.8; p = 0.21). Our findings further suggested that eliminating obesity and improving access to education may reduce DM cases by up to one third for the population at large (31.7% and 26.8%, respectively) and up to half (46.9% and 49.3%, respectively) for Qatari nationals. Promoting physical activity may reduce the burden of DM by up to 9.4% for the population at large and up to 17.3% for Qatari nationals. Conclusions: Demographic/lifestyle factors appear to be the main risk factors for the high DM levels observed in Qatar, with a contribution that outweighs that of genetic risk factors. While further evaluation of DM risk factors among the Qatari population (as opposed to the resident population) is important and of interest, these findings highlight the need to focus short-term DM interventions on addressing demographic/lifestyle risk factors to achieve substantial and timely declines in DM levels.
PMCID: PMC4344980  PMID: 25745596
epidemiology; diabetes mellitus; demographic factors; lifestyle; Qatar; Middle East; North Africa
6.  The effect of non-exercise activity thermogenesis on subjects with metabolic syndrome – a proof of concept study in Qatar 
Qatar Medical Journal  2013;2013(1):12-18.
Metabolic syndrome is a cluster of metabolic abnormalities that increases the risk of cardiovascular disease and type 2 diabetes. Total human energy expenditure is divided into three major components; resting metabolic rate, thermic effect of food, and activity thermogenesis which is divided into exercise and non exercise activity thermogenesis (NEAT). In this study, NEAT was used as a lifestyle intervention on subjects with metabolic syndrome. 200 eligible patients from the Diabetes and Endocrinology Department at Hamad Medical Hospital in Doha, Qatar were assigned to an intervention (n = 100) or control (n = 100) group and followed for one year. The intervention group was advised to practice NEAT enhancing activities, while the control group was not advised about NEAT. Measurements of waist circumference, weight, BMI, blood pressure, glucose and lipid profile were assessed at baseline, six months and 1 year.
After 1 year 52 intervention and 55 control subjects completed the study. The results revealed no statistically significant differences in metabolic syndrome components between the two randomized groups. The amount of recommended NEAT activity appears to have been too small to influence study outcomes. Future studies in similar populations may need to consider the high dropout rate, and use of incentives or other interventions to increase compliance and retention.
PMCID: PMC3991052  PMID: 25003052
7.  Ethnic and gender differences in advanced glycation end products measured by skin auto-fluorescence 
Dermato-endocrinology  2013;5(2):325-330.
Advanced glycation end products (AGEs) have been shown to be a predictor of cardiovascular risk in Caucasian subjects. In this study we examine whether the existing reference values are useable for non-Caucasian ethnicities. Furthermore, we assessed whether gender and smoking affect AGEs.
AGEs were determined by a non-invasive method of skin auto-fluorescence (AF). AF was measured in 200 Arabs, 99 South Asians, 35 Filipinos and 14 subjects of other/mixed ethnicity in the Qatar Metabolomics Study on Diabetes (QMDiab). Using multivariate linear regression analysis and adjusting for age and type 2 diabetes, we assessed whether ethnicity, gender and smoking were associated with AF.
The mean AF was 2.27 arbitrary units (AU) (SD: 0.63). Arabs and Filipinos had a significant higher AF than the South Asian population (0.25 arbitrary units (AU) (95% CI: 0.11‒0.39), p = 0.001 and 0.34 (95% CI: 0.13‒0.55), p = 0.001 respectively). Also, AF was significantly higher in females (0.41 AU (95% CI: 0.29‒0.53), p < 0.001). AF associated with smoking (0.21 AU (95% CI: 0.01‒0.41), p = 0.04) and increased with the number of pack-years smoked (p = 0.02).
This study suggests that the existing reference values should take ethnicity, gender and smoking into account. Larger studies in specific ethnicities are necessary to create ethnic- and gender-specific reference values.
PMCID: PMC3772922  PMID: 24194974
skin auto-fluorescence; advanced glycation endproducts; type 2 diabetes; gender differences; ethnicity; smoking; epidemiology
8.  Measuring Burden of Diseases in a Rapidly Developing Economy: State of Qatar 
Global Journal of Health Science  2012;5(2):134-144.
The Global Burden of Disease (GBD) study has provided a conceptual and methodological framework to quantify and compare the health of populations.
The objective of the study was to assess the national burden of disease in the population of Qatar using the disability-adjusted life year (DALYs) as a measure of disability.
We adapted the methodology described by the World Health Organization for conducting burden of disease to calculate years of life lost due to premature mortality (YLL), years lived with disability (YLD) and disability adjusted life years (DALYs). The study was conducted during the period from November 2011 to October 2012.
The study findings revealed that ischemic heart disease (11.8%) and road traffic accidents (10.3%) were the two leading causes of burden of diseases in Qatar in 2010. The burden of diseases among men (222.04) was found three times more than of women's (71.85). Of the total DALYs, 72.7% was due to non fatal health outcomes and 27.3% was due to premature death. For men, chronic diseases like ischemic heart disease (15.7%) and road traffic accidents (13.7%) accounted great burden and an important source of lost years of healthy life. For women, birth asphyxia and birth trauma (12.6%) and abortion (4.6%) were the two leading causes of disease burden.
The results of the study have shown that the national health priority areas should cover cardiovascular diseases, road traffic accidents and mental health. The burden of diseases among men was three times of women's.
PMCID: PMC4776792  PMID: 23445701
DALY; YLD; YLL; disability; mortality; incidence
9.  Comparison of Efficacy and Safety of Rosuvastatin, Atorvastatin and Pravastatin among Dyslipidemic Diabetic Patients 
ISRN Pharmacology  2013;2013:146579.
Objectives. To investigate the efficacy and the safety of the three most commonly prescribed statins (rosuvastatin, atorvastatin, and pravastatin) for managing dyslipidemia among diabetic patients in Qatar. Subjects and Methods. This retrospective observational population-based study included 350 consecutive diabetes patients who were diagnosed with dyslipidemia and prescribed any of the indicated statins between September 2005 and September 2009. Data was collected by review of the Pharmacy Database, the Electronic Medical Records Database (EMR viewer), and the Patient's Medical Records. Comparisons of lipid profile measurements at baseline and at first- and second-year intervals were taken. Results. Rosuvastatin (10 mg) was the most effective at reducing LDL-C (29.03%). Atorvastatin reduced LDL-C the most at a dose of 40 mg (22.8%), and pravastatin reduced LDL-C the most at a dose of 20 mg (20.3%). All three statins were safe in relation to muscular and hepatic functions. In relation to renal function, atorvastatin was the safest statin as it resulted in the least number of patients at the end of 2 years of treatment with the new onset of microalbuminuria (10.9%) followed by rosuvastatin (14.3%) and then pravastatin (26.6%). Conclusion. In the Qatari context, the most effective statin at reducing LDL-C was rosuvastatin 10 mg. Atorvastatin was the safest statin in relation to renal function. Future large-scale prospective studies are needed to confirm these results.
PMCID: PMC3582048  PMID: 23476802
10.  Exome Sequencing of Only Seven Qataris Identifies Potentially Deleterious Variants in the Qatari Population 
PLoS ONE  2012;7(11):e47614.
The Qatari population, located at the Arabian migration crossroads of African and Eurasia, is comprised of Bedouin, Persian and African genetic subgroups. By deep exome sequencing of only 7 Qataris, including individuals in each subgroup, we identified 2,750 nonsynonymous SNPs predicted to be deleterious, many of which are linked to human health, or are in genes linked to human health. Many of these SNPs were at significantly elevated deleterious allele frequency in Qataris compared to other populations worldwide. Despite the small sample size, SNP allele frequency was highly correlated with a larger Qatari sample. Together, the data demonstrate that exome sequencing of only a small number of individuals can reveal genetic variations with potential health consequences in understudied populations.
PMCID: PMC3490971  PMID: 23139751
11.  Plantar Temperature Response to Walking in Diabetes with and without Acute Charcot: The Charcot Activity Response Test 
Journal of Aging Research  2012;2012:140968.
Objective. Asymmetric plantar temperature differences secondary to inflammation is a hallmark for the diagnosis and treatment response of Charcot foot syndrome. However, little attention has been given to temperature response to activity. We examined dynamic changes in plantar temperature (PT) as a function of graduated walking activity to quantify thermal responses during the first 200 steps. Methods. Fifteen individuals with Acute Charcot neuroarthropathy (CN) and 17 non-CN participants with type 2 diabetes and peripheral neuropathy were recruited. All participants walked for two predefined paths of 50 and 150 steps. A thermal image was acquired at baseline after acclimatization and immediately after each walking trial. The PT response as a function of number of steps was examined using a validated wearable sensor technology. The hot spot temperature was identified by the 95th percentile of measured temperature at each anatomical region (hind/mid/forefoot). Results. During initial activity, the PT was reduced in all participants, but the temperature drop for the nonaffected foot was 1.9 times greater than the affected side in CN group (P = 0.04). Interestingly, the PT in CN was sharply increased after 50 steps for both feet, while no difference was observed in non-CN between 50 and 200 steps. Conclusions. The variability in thermal response to the graduated walking activity between Charcot and non-Charcot feet warrants future investigation to provide further insight into the correlation between thermal response and ulcer/Charcot development. This stress test may be helpful to differentiate CN and its response to treatment earlier in its course.
PMCID: PMC3413979  PMID: 22900177
12.  The utility of an electronic adherence assessment device in type 2 diabetes mellitus: a pilot study of single medication 
The primary objective of this pilot study was to determine if the Medication Event Monitoring System (MEMS) is capable of providing meaningful estimates of compliance within the indigenous Qatari population. The secondary objective was to highlight any specific problems which might be associated with the use of MEMS within this population.
A sample of adult diabetic Qatari patients attending an outpatient diabetic clinic were administered a Knowledge, Attitude, and Practices (KAP) questionnaire and then dispensed one of their regular medications in a MEMS®-fitted bottle. Data contained in the MEMS® were downloaded after the patients returned for a refill and adherence was estimated using 2 methods: pill count and MEMS® data.
A total of 54 patients agreed to participate in this pilot study. Adherence to daily doses was 67.7% and with regimen 13.7%. No correlation was found between adherence assessed by pill count and MEMS®. The association between KAP and adherence was generally poor. A number of other issues and challenges in the use of MEMS® that could affect its utility were noted and will be discussed.
Our results revealed problems associated with the use of MEMS® that could affect its usefulness in assessing adherence in this part of the world. Some issues identified in this pilot study included retrieving the MEMS®, registering extra opening of MEMS®, desire to hoard medicine by taking doses at different frequency than recorded in MEMS®. All these issues could be closely associated with the attitudes and practices of the patients, as demonstrated by our KAP analysis and correlations.
PMCID: PMC2915557  PMID: 20694184
Medication Events Monitoring System (MEMS); type 2 diabetes mellitus; drug therapy; medication adherence

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