scholarly journals SARS-CoV-2 susceptibility and ACE2 gene variations within diverse ethnic backgrounds

2021 ◽  
Author(s):  
Nirmal Vadgama ◽  
Alexander Kreymerman ◽  
Jackie Campbell ◽  
Olga Shamardina ◽  
Christiane Brugger ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Disease Susceptibility ◽  
Ethnically Diverse ◽  
European Population ◽  
East Asians ◽  
Receptor Affinity ◽  
The United Kingdom ◽  
Ethnic Comparisons ◽  
Protein Variants ◽  
Ace2 Gene

Background Host genetics play a major role in COVID-19 susceptibility and severity. Here, we analyse an ethnically diverse cohort of National Health Service (NHS) patients in the United Kingdom (UK) to assess the association between variants in the ACE2 locus and COVID-19 risk. Methods We analysed whole-genome sequencing (WGS) data of 6,274 participants who were tested for SARS-CoV-2 from the UK's 100,000 Genomes Project (100KGP) for the presence of ACE2 variants and expression quantitative trait loci (eQTLs). Findings We identified a splice site variant (rs2285666) associated with increased ACE2 expression with an overrepresentation in SARS-CoV-2 positive patients relative to 100KGP controls (p = .015), and in hospitalised European patients relative to outpatients in intra-ethnic comparisons (p = .029). We also compared the prevalence of 288 eQTLs, of which 23 were enriched in SARS-CoV-2 positive patients. The eQTL rs12006793 had the largest effect size (d = 0.91), which decreases ACE2 expression and is more prevalent in controls, thus potentially reducing risk of COVID-19. We identified three novel nonsynonymous variants predicted to alter ACE2 function, and showed that three variants (p.K26R, p.H378R, p.Y515N) alter receptor affinity for the viral Spike (S) protein. Variants p.K26R and p.N720D are more prevalent in the European population (p < .001), but Y497H is less prevalent compared to East Asians (p = .020). Interpretation Our results demonstrate that the spectrum of genetic variants in ACE2 may inform risk stratification of COVID-19 patients and could partially explain the differences in disease susceptibility and severity among different ethnic groups. Funding The 100KGP is funded by the National Institute for Health Research and NHS England. Funding was also obtained from Stanford University, Palo Alto.

scholarly journals Common genetic variants and pathways in diabetes and associated complications and vulnerability of populations with different ethnic origins

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sabrina Samad Shoily ◽  
Tamim Ahsan ◽  
Kaniz Fatema ◽  
Abu Ashfaqur Sajib
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Kidney Disease ◽  
Genetic Variants ◽  
Nucleotide Polymorphisms ◽  
Differential Distribution ◽  
East Asians ◽  
Single Nucleotide ◽  
Common Genetic Variants ◽  
Haplotype Frequencies ◽  
Variant Alleles

AbstractDiabetes mellitus is a complex and heterogeneous metabolic disorder which is often pre- or post-existent with complications such as cardiovascular disease, hypertension, inflammation, chronic kidney disease, diabetic retino- and nephropathies. However, the frequencies of these co-morbidities vary among individuals and across populations. It is, therefore, not unlikely that certain genetic variants might commonly contribute to these conditions. Here, we identified four single nucleotide polymorphisms (rs5186, rs1800795, rs1799983 and rs1800629 in AGTR1, IL6, NOS3 and TNFA genes, respectively) to be commonly associated with each of these conditions. We explored their possible interplay in diabetes and associated complications. The variant allele and haplotype frequencies at these polymorphic loci vary among different super-populations (African, European, admixed Americans, South and East Asians). The variant alleles are particularly highly prevalent in different European and admixed American populations. Differential distribution of these variants in different ethnic groups suggests that certain drugs might be more effective in selective populations rather than all. Therefore, population specific genetic architectures should be considered before considering a drug for these conditions.

Interaction Design for Inclusive Learning

2010 ◽  
pp. 28-40 ◽  
Author(s):  
Deryn Graham ◽  
Ian Benest ◽  
Peter Nicholl
Keyword(s):  
Interaction Design ◽  
Teaching And Learning ◽  
Large Scale ◽  
European Population ◽  
The United Kingdom ◽  
Inclusive Learning ◽  
All Solutions ◽  
Funded Project ◽  
Visually Impaired Students

The findings for a case study on improving interaction design for teaching visually impaired students, in an inclusive learning environment, are presented. The crux of the problem is the ability to draw and understand diagrams. The cognitive issues are often underestimated with insufficient attention being given to the use of metaphors, etc. and “one size fits all solutions” are often the norm. The findings of the original seed funded project, which was conducted by three universities in the United Kingdom, have led to design criteria and to an application for a large scale project, to produce generic tools and to enable “multi-modal” teaching and learning, with connotations for the support of people with cognitive as well as physical impairments, especially relevant with respect to an increasingly ageing European population.

scholarly journals Evaluation of the Influence of Genetic Variants of SLC2A9 (GLUT9) and SLC22A12 (URAT1) on the Development of Hyperuricemia and Gout

2020 ◽  
Vol 9 (8) ◽  
pp. 2510
Author(s):  
Katerina Pavelcova ◽  
Jana Bohata ◽  
Marketa Pavlikova ◽  
Eliska Bubenikova ◽  
Karel Pavelka ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Uric Acid ◽  
Genetic Variants ◽  
Biochemical Parameters ◽  
Previous Analysis ◽  
Direct Sequencing ◽  
Low Frequency ◽  
European Population ◽  
The Body ◽  
Genes Encoding

Urate transporters, which are located in the kidneys, significantly affect the level of uric acid in the body. We looked at genetic variants of genes encoding the major reabsorption proteins GLUT9 (SLC2A9) and URAT1 (SLC22A12) and their association with hyperuricemia and gout. In a cohort of 250 individuals with primary hyperuricemia and gout, we used direct sequencing to examine the SLC22A12 and SLC2A9 genes. Identified variants were evaluated in relation to clinical data, biochemical parameters, metabolic syndrome criteria, and our previous analysis of the major secretory urate transporter ABCG2. We detected seven nonsynonymous variants of SLC2A9. There were no nonsynonymous variants of SLC22A12. Eleven variants of SLC2A9 and two variants of SLC22A12 were significantly more common in our cohort than in the European population (p = 0), while variants p.V282I and c.1002+78A>G had a low frequency in our cohort (p = 0). Since the association between variants and the level of uric acid was not demonstrated, the influence of variants on the development of hyperuricemia and gout should be evaluated with caution. However, consistent with the findings of other studies, our data suggest that p.V282I and c.1002+78A>G (SLC2A9) reduce the risk of gout, while p.N82N (SLC22A12) increases the risk.

scholarly journals Mental Health During COVID-19: A Qualitative Study with Ethnically Diverse Healthcare Workers in the United Kingdom

2021 ◽  
Author(s):  
Irtiza Qureshi ◽  
Mayuri Gogoi ◽  
Amani Al-Oraibi ◽  
Fatimah Wobi ◽  
Jonathan Chaloner ◽  
...  
Keyword(s):  
Mental Health ◽  
United Kingdom ◽  
Ethnic Minority ◽  
Healthcare Workers ◽  
Negative Impact ◽  
Ethnically Diverse ◽  
Working Hours ◽  
Severe Illness ◽  
List Type ◽  
The United Kingdom

ABSTRACTIntroductionHealthcare workers are experiencing deterioration in their mental health due to COVID-19. Ethnic minority populations in the United Kingdom are disproportionately affected by COVID-19, with a higher death rate and poorer physical and mental health outcomes. It is important that healthcare organisations consider the specific context and mental, as well as physical, health needs of an ethnically diverse healthcare workforce in order to better support them during, and after, the COVID-19 pandemic.MethodsWe undertook a qualitative work package as part of the United Kingdom Research study into Ethnicity and COVID-19 outcomes among healthcare workers (UK-REACH). As part of the qualitative research, we conducted focus group discussions with healthcare workers between December 2020 and July 2021, and covered topics such as their experiences, fears and concerns, and perceptions about safety and protection, while working during the pandemic. The purposive sample included ancillary health workers, doctors, nurses, midwives and allied health professionals from diverse ethnic backgrounds. We conducted discussions using Microsoft Teams. Recordings were transcribed and thematically analysed.FindingsWe carried out 16 focus groups with a total of 61 participants. Several factors were identified which contributed to, and potentially exacerbated, the poor mental health of ethnic minority healthcare workers during this period including anxiety (due to inconsistent protocols and policy); fear (of infection); trauma (due to increased exposure to severe illness and death); guilt (of potentially infecting loved ones); and stress (due to longer working hours and increased workload).ConclusionCOVID-19 has affected the mental health of healthcare workers. We identified a number of factors which may be contributing to a deterioration in mental health across diverse ethnic groups. Healthcare organisations should consider developing strategies to counter the negative impact of these factors. This paper will help employers of healthcare workers and other relevant policy makers better understand the wider implications and potential risks of COVID-19 and assist in developing strategies to safeguard the mental health of these healthcare workers going forward, and reduce ethnic disparities.Key messagesWhat is already known about this subjectHealthcare Workers (HCWs) are experiencing deterioration of their mental health due to COVID-19Ethnic minority populations and HCWs are disproportionately affected by COVID-19More research is needed on the specific factors influencing the mental health of ethnically diverse healthcare workforcesWhat are the new findingsProminent factors influencing the mental health and emotional wellbeing of this population include:anxiety (due to inconsistent protocols and policy)fear (of infection)trauma (due to increased exposure to severe illness and death)guilt (of potentially infecting loved ones)stress (due to longer working hours and increased workload)How might this impact on policy or clinical practice in the foreseeable futureHealthcare organisations should consider the specific circumstances of these staff and develop strategies to counter the negative impact of these factors and help safeguard the mental health of their staff

scholarly journals Large-scale clinical interpretation of genetic variants using evolutionary data and deep learning

2020 ◽  
Author(s):  
Jonathan Frazer ◽  
Pascal Notin ◽  
Mafalda Dias ◽  
Aidan Gomez ◽  
Kelly Brock ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Large Scale ◽  
Protein Sequences ◽  
Evolutionary Model ◽  
Generative Models ◽  
Evolutionary Information ◽  
Disease Genes ◽  
Independent Evidence ◽  
Variants Of Unknown Significance ◽  
Protein Variants

AbstractQuantifying the pathogenicity of protein variants in human disease-related genes would have a profound impact on clinical decisions, yet the overwhelming majority (over 98%) of these variants still have unknown consequences1–3. In principle, computational methods could support the large-scale interpretation of genetic variants. However, prior methods4–7 have relied on training machine learning models on available clinical labels. Since these labels are sparse, biased, and of variable quality, the resulting models have been considered insufficiently reliable8. By contrast, our approach leverages deep generative models to predict the clinical significance of protein variants without relying on labels. The natural distribution of protein sequences we observe across organisms is the result of billions of evolutionary experiments9,10. By modeling that distribution, we implicitly capture constraints on the protein sequences that maintain fitness. Our model EVE (Evolutionary model of Variant Effect) not only outperforms computational approaches that rely on labelled data, but also performs on par, if not better than, high-throughput assays which are increasingly used as strong evidence for variant classification11–23. After thorough validation on clinical labels, we predict the pathogenicity of 11 million variants across 1,081 disease genes, and assign high-confidence reclassification for 72k Variants of Unknown Significance8. Our work suggests that models of evolutionary information can provide a strong source of independent evidence for variant interpretation and that the approach will be widely useful in research and clinical settings.

scholarly journals Evidence of polygenic selection on human stature inferred from spatial distribution of allele frequencies

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 15 ◽  
Author(s):  
Davide Piffer
Keyword(s):  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Average Frequency ◽  
Allele Frequencies ◽  
Genome Wide Association ◽  
East Asians ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
Human Height ◽  
Polygenic Selection

Spatial patterns of allele frequencies reveal a clear signal of natural (or sexual) selection on human height. The average frequency of 66 common genetic variants for 26 populations belonging to 5 sub-continental human groups was significantly correlated to average phenotypic population height. The method of correlated vectors provided additional evidence for a signal of natural selection in SNPs with higher significance. Factor analysis of the five top genome-wide association study (GWAS) hits revealed a clear factor indicating selection pressures on human height, peaking among northern Europeans and some African groups (Esan Nigeria) whilst reaching a nadir among South-East Asians.

scholarly journals SARS-CoV-2 Receptor and Renin-Angiotensin System Regulation: Impact of Genetics Variants in ACE2 Gene Impact of Genetics Variants in the ACE2 Gene in the Functional Receptor of SARS-CoV-2

2020 ◽  
Vol 5 (7) ◽  
pp. 489-497
Author(s):  
Juliana de Oliveira Cruz ◽  
Sandra Mara Bispo Sousa
Keyword(s):  
Protein Binding ◽  
Genetic Variants ◽  
Evolutionary Relationship ◽  
Physiological Role ◽  
Renin Angiotensin System ◽  
Spike Protein ◽  
Human Populations ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ace2 Gene

The ACE2 has a physiological role in the regulation of the Renin-Angiotensin System. It is also described your function as a receptor for SARS-CoV-2 and other coronaviruses. Genetic variants in ACE2 are associated with cardiovascular diseases in different human populations and drug response. There is no direct evidence that mutations in ACE2 confer resistance to coronavirus spike protein binding. The evolutionary relationship between spike protein binding and ACE2 is complex. Significant genetic variants are present in ACE2, meanwhile, the evolutionary time of contact of the human ACE2 to the virus is short and, therefore, it did not suffer sufficient selective pressures to offer resistance to viral spike protein binding at the population level. More efforts are needed to identify genetic variants in human ACE2 and other genes, and, consequently, conducting case-control studies to validate these variants and their possible association with infection rates by SARS-CoV-2 and/or clinical outcome.

Sign in / Sign up

Export Citation Format

Share Document