Factors that influence a patient’s decision to engage in genetic research

IntroductionThe most challenging step in clinical research studies is patient recruitment. Many research studies do not reach their targets because of participant rejection. The purpose of this study was to assess patient as well as the community knowledge, motivation, and barriers to participate in genetic research.MethodsA cross-section study was conducted between September 2018 and February 2020 using face-to-face interviews with candidate patients from outpatient clinics at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia. Additionally, an online survey was conducted to assess the community’s knowledge, motivation and barriers to participate in genetic research studies.ResultsIn total, 470 patients were interviewed for this study, with 341 being successfully recruited for the face to face interview, and the other patients being refused owing to time constraints. The majority percentage of the respondents were females. The respondents’ mean age was 30, and 52.6% reported having a college degree. The survey results from 388 participants illustrated that around 90% of the participants, participated voluntarily due to a good understanding of genetics studies. The majority held positive attitudes toward being part of genetic research, which exceeded the reported motivation score of >75%. The survey indicated that >90% of individuals were willing to participate to acquire therapeutic benefits or to receive continued aftercare. However, 54.6% of survey participants were worried about the side effects and the risks involved in genetic testing. A higher proportion (71.4%) of respondents reported that lack of knowledge about genetic research was one of the barriers to rejecting participation.ConclusionRespondents reported relatively high motivation and knowledge for participation in genetic research. However, study participants reported “do not know enough about genetic research” and “lack of time during clinic visit” as a barrier for participation in genetic research

Exome-wide association study to identify rare variants influencing COVID-19 outcomes : Results from the Host Genetics Initiative

Publisher Copyright: Copyright: © 2022 Butler-Laporte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.Peer reviewe

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

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Use of Rapid COVID-19 Antibody Testing to Evaluate Relative Risk of Infection in Campus Versus Non-campus Residents at a Government Institution in Saudi Arabia: a Cohort Study

Abstract Background: The World Health Organization confirmed in January 2020 that SARS-CoV-2 has become a pandemic infection. The first case in Saudi Arabia was reported on March 2, 2020. The Saudi Ministry of Health has authorized the use of anti-SARS-CoV-2 immunoglobulin M/immunoglobulin G (IgM/IgG) antibody testing, but serological test evaluations are still ongoing. Methods: The primary study aim was to determine whether living on a government institution campus, thus limiting contact with the general public, protects against SARS-CoV-2 infection. A study population of 763 employees of the King Abdulaziz City for Science and Technology (KACST) in Saudi Arabia and their family members were asked about their age, nationality, residency on or off the KACST campus, chronic conditions, previous COVID-19 symptoms, exposure to infected individuals, and COVID-19 PCR test results. After informed consent was obtained, the VivaDiagTM COVID-19 IgM/IgG Rapid Test was administered. Statistical analysis was conducted of Pearson correlation coefficients for, and generalized linear regression model fitting for predictive ability of, several independent variables versus IgG status. Results: While the study population was skewed towards male, Saudi nationality, and younger individuals, the age distribution was similar between on-campus residents and off-campus residents. Of the 763 study individuals 91.1% were non-campus residents and 8.9% were campus residents. Discussion: As expected, being IgG+ strongly positively correlated with having the COVID-19 symptom of loss of smell (r = 0.417052483). On-campus residency weakly or somewhat correlated with being IgG positive (IgG+; r = 0.187990064) or IgM positive (IgM+; r= 0.242302626), indicating that residing on campus actually increased the risk of SARS-CoV-2 infection. Consistent with this, residency status was highly statistically significantly predictive (p = 0.00002) of IgG status, second only to contact with a COVID19 infected individual (p = 0.00000), and living on campus increased the likelihood of being IgG+. Blood type (p = 0.01069), loss of sense of smell (p = 0.01079); hypertension (p = 0.01871), nationality (p = 0.02324), and PCR test status (p = 0.04243) also statistically significantly predicted IgG status.Conclusions: Contrary to the hypothesis, living on campus actually increased the risk of testing positive for IgG antibodies against SARS-CoV-2 infection.</jats:p

MBCL-01. METHYLATION PROFILING OF PEDIATRIC MEDULLOBLASTOMA IN SAUDI ARABIA IN A CLINICAL SETTING PERMITS SUB-CLASSIFICATION AND REVEALS NEW OUTCOME PREDICTIONS

Abstract Medulloblastoma (MB) is the most common childhood malignant brain tumor. DNA methylation profiling has rapidly advanced our understanding of MB pathogenesis at the molecular level, MBs can be sub-grouped according to methylation patterns from FPPE samples into Wingless (WNT-MB), Sonic Hedgehog (SHH-MB), Group 3 (G3) and Group 4 (G4) WNT-MB and SHH-MB subgroups are characterized by gain-of function mutations that activate oncogenic cell signalling whilst G3/G4 tumors show recurrent chromosomal alterations. each subgroup has distinct clinical outcomes, the ability to subgroup SA-FPPE samples holds significant prognostic and therapeutic value. We performed the first assessment of MB-DNA methylation patterns in Saudi Arabian SA cohort using archival biopsy materials (FPPE n=49). Of the 41 materials available for methylation assessments, 39 could be classified into the major DNA methylation subgroups (SHH, WNT, G3 and G4). Methylation analysis was able to reclassify tumors that could not be sub-grouped through NGS testing, highlighting its improved accuracy for MB molecular classifications. Independent assessments demonstrate clinical relationships of the subgroups, exemplified by the high survival rates observed for WNT tumors. Surprisingly, the G4 subgroup did not conform to previously identified phenotypes, with a high prevalence in females, high metastatic rates and a large number of tumor-associated deaths. DNA methylation profiling enables the robust sub-classification of four disease sub-groups in SA-MB patients. Moreover, the incorporation of DNA methylation biomarkers can significantly improve current disease-risk stratification schemes, particularly concerning the identification of aggressive G4 tumors. These findings have important implications for future clinical disease management in MB cases across the Arab world.</jats:p

Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative.

Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights

Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative

AbstractHost genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p=5.41×10−7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.Author SummaryCOVID-19 clinical outcomes vary immensely, but a patient’s genetic make-up is an important determinant of how they will fare against the virus. While many genetic variants commonly found in the populations were previously found to be contributing to more severe disease by the COVID-19 Host Genetics Initiative, it isn’t clear if more rare variants found in less individuals could also play a role. This is important because genetic variants with the largest impact on COVID-19 severity are expected to be rarely found in the population, and these rare variants require different technologies to be studies (usually whole-exome or whole-genome sequencing). Here, we combined sequencing results from 21 cohorts across 12 countries to perform a rare variant association study. In an analysis comprising 5,085 participants with severe COVID-19 and 571,737 controls, we found that the gene for toll-like receptor 7 (TLR7) on chromosome X was an important determinant of severe COVID-19. Importantly, despite being found on a sex chromosome, this observation was consistent across both sexes.</jats:sec

Exome-wide association study to identify rare variants influencing COVID-19 outcomes : Results from the Host Genetics Initiative

Publisher Copyright: Copyright: © 2022 Butler-Laporte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.Peer reviewe