Epigenetic associations of type 2 diabetes and BMI in an Arab population

Background The prevalence of type 2 diabetes (T2D) and obesity has dramatically increased within a few generations, reaching epidemic levels. In addition to genetic risk factors, epigenetic mechanisms triggered by changing environment are investigated for their role in the pathogenesis of these complex diseases. Epigenome-wide association studies (EWASs) have revealed significant associations of T2D, obesity, and BMI with DNA methylation. However, populations from the Middle East, where T2D and obesity rates are highest worldwide, have not been investigated so far. Methods We performed the first EWAS in an Arab population with T2D and BMI and attempted to replicate 47 EWAS associations previously reported in Caucasians. We used the Illumina Infinium HumanMethylation450 BeadChip to quantify DNA methylation in whole blood DNA from 123 subjects of 15 multigenerational families from Qatar. To investigate the effect of differing genetic background and environment on the epigenetic associations, we further assessed the effect of replicated loci in 810 twins from UK. Results Our EWAS suggested a novel association between T2D and cg06721411 (DQX1; p value = 1.18 × 10−9). We replicated in the Qatari population seven CpG associations with BMI (SOCS3, p value = 3.99 × 10−6; SREBF1, p value = 4.33 × 10−5; SBNO2, p value = 5.87 × 10−5; CPT1A, p value = 7.99 × 10−5; PRR5L, p value = 1.85 × 10−4; cg03078551, intergenic region on chromosome 17; p value = 1.00 × 10−3; LY6G6E, p value = 1.10 × 10−3) and one with T2D (TXNIP, p value = 2.46 × 10−5). All the associations were further confirmed in the UK cohort for both BMI and T2D. Meta-analysis increased the significance of the observed associations and revealed strong heterogeneity of the effect sizes (apart from CPT1A), although associations at these loci showed concordant direction in the two populations. Conclusions Our study replicated eight known CpG associations with T2D or BMI in an Arab population. Heterogeneity of the effects at all loci except CPT1A between the Qatari and UK studies suggests that the underlying mechanisms might depend on genetic background and environmental pressure. Our EWAS results provide a basis for comparison with other ethnicities

Unilateral optic neuropathy following subdural hematoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Unilateral optic neuropathy is commonly due to a prechiasmatic affliction of the anterior visual pathway, while losses in visual hemifields result from the damage to brain hemispheres. Here we report the unusual case of a patient who suffered from acute optic neuropathy following hemispherical subdural hematoma. Although confirmed up to now only through necropsy studies, our case strongly suggests a local, microcirculatory deficit identified through magnetic resonance imaging <it>in vivo</it>.</p> <p>Case presentation</p> <p>A 70-year-old Caucasian German who developed a massive left hemispheric subdural hematoma under oral anticoagulation presented with acute, severe visual impairment on his left eye, which was noticed after surgical decompression. Neurologic and ophthalmologic examinations indicated sinistral optic neuropathy with visual acuity reduced nearly to amaurosis. Ocular pathology such as vitreous body hemorrhage, papilledema, and central retinal artery occlusion were excluded. An orbital lesion was ruled out by means of orbital magnetic resonance imaging. However, cerebral diffusion-weighted imaging and T2 maps of magnetic resonance imaging revealed a circumscribed ischemic lesion within the edematous, slightly herniated temporomesial lobe within the immediate vicinity of the affected optic nerve. Thus, the clinical course and morphologic magnetic resonance imaging findings suggest the occurrence of pressure-induced posterior ischemic optic neuropathy due to microcirculatory compromise.</p> <p>Conclusion</p> <p>Although lesions of the second cranial nerve following subdural hematoma have been reported individually, their pathogenesis was preferentially proposed from autopsy studies. Here we discuss a dual, pressure-induced and secondarily ischemic pathomechanism on the base of <it>in vivo </it>magnetic resonance imaging diagnostics which may remain unconsidered by computed tomography.</p

Recurrent neural networks for enhanced joint channel estimation and interference cancellation in FBMC and OFDM systems: unveiling the potential for 5G networks

Abstract FBMC is a pivotal system in 5G, serving as a cornerstone for efficient use of available bandwidth while simultaneously meeting stringent requirements for high spectral efficiency. Notably, FBMC harnesses the power of multicarrier modulation (MC), a good alternative to orthogonal frequency division multiplexing (OFDM) technology that supports fourth-generation (4G) systems. The wireless communications field is full of challenges, the most important of which are channel estimation and interference cancellation, both of which deserve comprehensive study to increase the efficiency of data transmission. In this paper, our investigation takes a deliberate step towards the convergence of two prominent modulation models: OFDM and FBMC. We specifically contrast these modulation techniques with the intricate field of joint channel estimation and interference cancellation (JCEIC). In this research study, we take advantage of recurrent neural networks' (RNNs') efficiency as a vehicular channel to perform precise channel estimation and recovery of uncorrupted transmitted signals, thereby lowering the bit error rate (BER). Our channel estimation for a dual selective channel is based on the thoughtful placement of pilots scattered over the temporal and frequency dimensions, and is further improved by the interference cancellation method of low complexity that was selected. Our JCEIC proposal aims to integrate RNNs carefully, using the output sequences of JCEIC algorithms as useful inputs to this neural architecture. By clearly demonstrating a decrease in BER as compared to traditional approaches, it is evident that the performance of the novel approach is near to that of a perfect channel. Additionally, a comparison of the performance of FBMC and OFDM systems at various signal-to-noise ratios reveals a clear performance divide that favors the former in terms of system efficiency. The BER is restricted by FBMC to a commendable threshold of less than 0.1 at a modest 5 dB, continuing the higher trend started by its improved RNN-based channel estimate. The accuracy of channel estimation is clearly improved by this paradigm shift, and the computing complexity typical of 5G networks is also clearly reduced

The Special Features of Prenatal and Preimplantation Genetic Counseling in Arab Countries.

Genetic counseling services have only recently been introduced in most Arab countries, and their utilization is increasing. Prenatal genetic counseling is essential, particularly in the Arab context, which is characterized by high rates of consanguinity. Nevertheless, little is known about the decisions faced by parents and the factors underlying the complex decision making that must occur when accessing these services in Arab countries. Herein, we performed a narrative review to discuss the reported experiences of parents accessing genetic counseling in the prenatal setting in the 22 Arab countries. We also highlight the different types of decisions encountered and the factors influencing them. We report that: (i) utilization of genetic counseling services varies across different Arab countries; (ii) many factors affect decision making and service utilization, especially religion; and (iii) parents are faced with an array of decisions in the prenatal setting, partly driven by increased utilization of prenatal diagnosis and preimplantation genetic testing in some countries. Our work is the first to highlight the different factors and decisions influencing genetic counseling in Arab countries. Understanding these factors is essential for improving genetic counseling services in the region and helping counselors facilitate informed decision making.This publication was supported by Qatar University, internal grant No. (QUST-1-CHS-2022-320). The findings achieved herein are solely the responsibility of the authors

Genetic epidemiology of Woodhouse-Sakati Syndrome in the Greater Middle East region and beyond: a systematic review

Background: Woodhouse-Sakati syndrome (WSS) is a rare, autosomal recessive genetic disorder with variable clinical manifestations mainly affecting the endocrine and nervous systems. The aim of this study was to systematically review the genetic basis of WSS and report the genetic variants and clinical phenotypes associated with the disease. Methods: PubMed, Science Direct, Scopus, and Web of Science databases were searched from the time of inception until June 2022. Broad search terms were used to capture the literature describing all genetic variants associated with WSS. The search keywords used are "Woodhouse Sakati" along with the term "mutation" OR "gene" OR "variant" OR "polymorphism". Results: Twenty-five eligible studies were included in this study. One hundred and eighty-five patients in 97 families from 12 different countries were diagnosed with WSS. In patients from the Greater Middle East (GME) region, consanguineous marriages were common (67%). Thirteen different DCAF17 variants were associated with WSS development (including 8 identified in the GME region). The most frequent variant was a frameshift deletion variant (c.436delC, p.Ala147Hisfs*9) unique to Arabs that was reported in 11 cases from Tunisia, Kuwait, Qatar, Bahrain, and Saudi Arabia. There were no clear genotype-phenotype correlations for the different variants. Conclusions: This systematic review highlights the molecular basis and clinical manifestations of WSS globally, including the GME region, where the disease is prevalent due to consanguinity. Additional studies are now needed to understand the genotype-phenotype correlation for different DCAF17 variants and their impact on the phenotypic heterogeneity observed in WSS patients. 2023, The Author(s).Scopu

Association of DNA methylation with age, gender, and smoking in an Arab population.

BACKGROUND: Modification of DNA by methylation of cytosines at CpG dinucleotides is a widespread phenomenon that leads to changes in gene expression, thereby influencing and regulating many biological processes. Recent technical advances in the genome-wide determination of single-base DNA-methylation enabled epigenome-wide association studies (EWASs). Early EWASs established robust associations between age and gender with the degree of CpG methylation at specific sites. Other studies uncovered associations with cigarette smoking. However, so far these studies were mainly conducted in Caucasians, raising the question of whether these findings can also be extrapolated to other populations. RESULTS: Here, we present an EWAS with age, gender, and smoking status in a family study of 123 individuals of Arab descent. We determined DNA methylation at over 450,000 CpG sites using the Illumina Infinium HumanMethylation450 BeadChip, applied state-of-the-art data processing protocols, including correction for blood cell type heterogeneity and hidden confounders, and eliminated probes containing SNPs at the targeted CpG site using 40&times; whole-genome sequencing data. Using this approach, we could replicate the leading published EWAS associations with age, gender and smoking, and recovered hallmarks of gender-specific epigenetic changes. Interestingly, we could even replicate the recently reported precise prediction of chronological age based on the methylation of only a few selected CpG sites. CONCLUSION: Our study supports the view that when applied with state-of-the art protocols to account for all potential confounders, DNA methylation arrays represent powerful tools for EWAS with more complex phenotypes that can also be successfully applied to non-Caucasian populations