Willingness to participate in genome testing: a survey of public attitudes from Qatar

Genomics has the potential to revolutionize medical approaches to disease prevention, diagnosis, and treatment, but it does not come without challenges. The success of a national population-based genome program, like the Qatar Genome Program (QGP), depends on the willingness of citizens to donate samples and take up genomic testing services. This study explores public attitudes of the Qatari population toward genetic testing and toward participating in the QGP. A representative sample of 837 adult Qataris was surveyed in May 2016. Approximately 71% of respondents surveyed reported that they were willing to participate in the activities of the QGP. Willingness to participate was significantly associated with basic literacy in genetics, a family history of genetic diseases, and previous experience with genetic testing through premarital screening. Respondents cited the desire to know more about their health status as the principle motivation for participating, while lack of time and information were reported as the most important barriers. With QGP plans to ramp up the scale of its national operation toward more integration into clinical care settings, it is critical to understand public attitudes and their determinants. The results demonstrate public support but also identify the need for more education and individual counseling that not only provide information on the process, challenges, and benefits of genomic testing, but that also address concerns about information security

Qatar genome: Insights on genomics from the Middle East

Despite recent biomedical breakthroughs and large genomic studies growing momentum, the Middle Eastern population, home to over 400 million people, is underrepresented in the human genome variation databases. Here we describe insights from Phase 1 of the Qatar Genome Program with whole genome sequenced 6047 individuals from Qatar. We identified more than 88 million variants of which 24 million are novel and 23 million are singletons. Consistent with the high consanguinity and founder effects in the region, we found that several rare deleterious variants were more common in the Qatari population while others seem to provide protection against diseases and have shaped the genetic architecture of adaptive phenotypes. These results highlight the value of our data as a resource to advance genetic studies in the Arab and neighboring Middle Eastern populations and will significantly boost the current efforts to improve our understanding of global patterns of human variations, human history, and genetic contributions to health and diseases in diverse populations.The Qatar Genome Program (QGP) and Qatar Biobank (QBB) are both Research and Development entities within Qatar Foundation for Education, Science and Community Development. The authors are thankful for everyone who contributed to this endeavor including the QGP and QBB team members, in addition to our partners at Hamad Medical Corporation (HMC), Sidra Medicine and other national stakeholders. The authors would like to especially thank all participants in this study for their continuous support

Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies

Towards a National Electronic Health Record in Qatar: Building on International Experiences

Background: During the past decade, the IT industry has introduced several new concepts within the health domain including e-health, electronic health record, digital hospital, and many more. Although each of these terms has brought its own unique definition and perspectives, they were all based on the foundation that healthcare and wellness management are dependent on effectively using technology to access accurate data in a timely fashion; ensuring enhanced patient care and medical error reduction. The Electronic Health Record (EHR) is an integrated system that collects data from different healthcare providers to create a unified electronic record for each patient among the population. Today, the patient's health information is scattered across different healthcare facilities causing significant inefficiencies within the healthcare system. A national EHR system will tackle these challenges by producing a personal health record for each patient, integrating information from all healthcare providers, and additionally giving access to patients themselves allowing their contribution. Motivation: There are many health IT implementations for EHR programs around the world that serve as great learning experiences for Qatar, offering it a great opportunity to leverage the best national EHR implementation strategies and practices. National EHR initiatives in Qatar emphasize the need to have secure electronic management of health data in structured and standardized formats, which can be communicated across its hospitals, primary healthcare centres, and other healthcare facilities. Personalized medicine initiatives share and extend these goals, with additional precision provided by genetic/genomic-based improved diagnostic, prognostic, and preventive information; thereby demanding a coordinated extension for the adoption and implementation requirements of an integrated national EHR system. It is for this purpose and understanding that the State of Qatar has taken the first concrete steps towards a promising EHR journey that will promote significant changes on how healthcare services are delivered, and more importantly, how each individual in Qatar can be empowered to become an active contributor to the management of their own health. In moving towards the widespread adoption and implementation of a national EHR system in Qatar, it is important to study the different challenges and trends used for the adoption of EHR systems, under national strategies, in other countries. This is essential for health informatics researchers, clinicians, and policy makers, to gain greater insight into the issues concerning the transformation of healthcare using a national EHR system. The results of this review study shall complement, explain, and extend the conclusions of earlier studies commissioned to explore the health information technology ecosystem in the State of Qatar. Objectives: The purpose of this study is to review EHR programs from various countries with regard to the issues documented in the studies commissioned in these countries. Our analysis will derive the most common critical aspects and lessons learned from international experiences during the implementation of national EHR programs. Additionally, it will explore opportunities, constraints, and characteristics present in Qatar, necessary for tailoring the strategies and approaches to fully realize a national EHR system in the country. This review study presents two important contributions: 1) it will significantly support promoting health IT solutions that are right for Qatar's need, recognizing the size and capabilities of the country, leveraging existing healthcare organizations and solutions, and respecting the unique cultural characteristics of its population. 2) it will serve as a baseline from which comparisons, performance against target measures, and forward thinking can be scoped; allowing significant contribution towards productive future development of health information technology and personalized medicine initiatives in Qatar. Methods: The data collection techniques included: (a) literature review for articles about EHR adoption under national strategies in several countries, (b) review of reports regarding national e-health strategy and government policies in Qatar, and (c) interviews of people participating in the policy making for national EHR system in Qatar (health and academic professionals involved in health IT research in Qatar). The reviewed EHR programs were selected according to the following criteria: (a) program for the implementation of national EHR system has been initiated since at least 5 years, (b) pilot projects have already been conducted, and (c) the planned EHR systems encompass various approaches of implementation. In line with these criteria, the EHR programs that have been studied were those of the following five countries: United States, England, Estonia, Japan, and Australia. Results: The analysis performed on the selected international EHR programs revealed many lessons learned, including: 1) To achieve a successful EHR implementation, it is critical to increase the awareness of the Qatari population about the upcoming changes in their healthcare experiences, paving the way to a smoother transition while having people's trust and confidence in the new system. 2) It is essential to legally define the legislation of privacy protection of personal medical data to support new e-health concepts and eliminate the risk of violating the privacy of patient data. 3) It is important to allow appropriate time for procurement, utilization, benefit realization and the complete project, otherwise you may risk having stakeholders and the public lose confidence in the EHR project. 4) Financial incentives for healthcare providers proved to be an effective method towards raising the EHR adoption rate. 5) To expedite EHR program acceptance, it is imperative to recruit knowledgeable and experienced technical staff and healthcare leaders, who encourage others to play a critical role during the transition process, and view this change as a dominantly positive one. 6) In order to make EHR an everyday tool for doctors, nurses, patients and public authorities, it is necessary to implement services based on the interests of the healthcare providers and society. 7) Continuous adjustment and enhancement is needed in order to sustain a successful and efficient system. Conclusion: Experiences from other countries suggest that a clear focus needs to be carefully placed on technical, clinical, organizational, financial, social, and patient perspectives to ensure that the full benefits of a national EHR system in Qatar can be realized. In addition, it demonstrates that strategic and human challenges are more difficult to master than technical aspects. The results of this review study can be used as a baseline to provide recommendations on how to tackle potential barriers towards successful adoption of a national EHR system in Qatar.qscienc

Willingness to participate in genome testing: a survey of public attitudes from Qatar

Genomics has the potential to revolutionize medical approaches to disease prevention, diagnosis, and treatment, but it does not come without challenges. The success of a national population-based genome program, like the Qatar Genome Program (QGP), depends on the willingness of citizens to donate samples and take up genomic testing services. This study explores public attitudes of the Qatari population toward genetic testing and toward participating in the QGP. A representative sample of 837 adult Qataris was surveyed in May 2016. Approximately 71% of respondents surveyed reported that they were willing to participate in the activities of the QGP. Willingness to participate was significantly associated with basic literacy in genetics, a family history of genetic diseases, and previous experience with genetic testing through premarital screening. Respondents cited the desire to know more about their health status as the principle motivation for participating, while lack of time and information were reported as the most important barriers. With QGP plans to ramp up the scale of its national operation toward more integration into clinical care settings, it is critical to understand public attitudes and their determinants. The results demonstrate public support but also identify the need for more education and individual counseling that not only provide information on the process, challenges, and benefits of genomic testing, but that also address concerns about information security.Other Information Published in: Journal of Human Genetics License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s10038-020-0806-y</p

The QChip1 knowledgebase and microarray for precision medicine in Qatar

Risk genes for Mendelian (single-gene) disorders (SGDs) are consistent across populations, but pathogenic risk variants that cause SGDs are typically population-private. The goal was to develop "QChip1," an inexpensive genotyping microarray to comprehensively screen newborns, couples, and patients for SGD risk variants in Qatar, a small nation on the Arabian Peninsula with a high degree of consanguinity. Over 108 variants in 8445 Qatari were identified for inclusion in a genotyping array containing 165,695 probes for 83,542 known and potentially pathogenic variants in 3438 SGDs. QChip1 had a concordance with whole-genome sequencing of 99.1%. Testing of QChip1 with 2707 Qatari genomes identified 32,674 risk variants, an average of 134 pathogenic alleles per Qatari genome. The most common pathogenic variants were those causing homocystinuria (1.12% risk allele frequency), and Stargardt disease (2.07%). The majority (85%) of Qatari SGD pathogenic variants were not present in Western populations such as European American, South Asian American, and African American in New York City and European and Afro-Caribbean in Puerto Rico; and only 50% were observed in a broad collection of data across the Greater Middle East including Kuwait, Iran, and United Arab Emirates. This study demonstrates the feasibility of developing accurate screening tools to identify SGD risk variants in understudied populations, and the need for ancestry-specific SGD screening tools. 2022, The Author(s).This is a collaborative work between Qatar Genome, Qatar Biobank, Weill Cornell (New York and Qatar), Hamad Medical Corporation and Sidra Medicine. We are thankful for everyone who contributed to this endeavor from all participating institutes. We would like to especially thank all participants in this study for their continuous support. We thank Dr. Fatemeh Abbaszadeh, for quality control and implementing QChip in the diagnostic services; N. Mohamed for editorial support, E. Betancourt for administrative support, E. Guzman for IT support, and J. Pillardy for high-performance computing support. J.R.F. also thanks Alan R. Shuldiner and Regeneron Genetics Center for supporting, J.R.F. to help complete this project. Special thanks to Alphonse Tharangeval at the Dasman Diabetes Institute in Kuwait for providing allele frequency lookups, and to the Center for Arab Genetic Studies in UAE, the GME Variome at University of California at San Diego and the Iranomefor providing public access to their databases. The authors are saddened by the passing of Andrew Brooks after the manuscript was submitted to the journal for review. This publication was made possible by The Qatar Foundation, the Weill Cornell Medical College in Qatar; NPRP 09-741-3 193, NPRP 5-436-3-116, NPRP 7-1425-3-370, NPRP 7-1301-3-336, and NPRP P8-1913-3-396 from the Qatar National Research Fund (a member of the Qatar Foundation). The findings achieved herein are solely the responsibility of the authors.Scopu

One Year of SARS-CoV-2: Genomic Characterization of COVID-19 Outbreak in Qatar

Qatar, a country with a strong health system and a diverse population consisting mainly of expatriate residents, has experienced two large waves of COVID-19 outbreak. In this study, we report on 2634 SARS-CoV-2 whole-genome sequences from infected patients in Qatar between March-2020 and March-2021, representing 1.5% of all positive cases in this period. Despite the restrictions on international travel, the viruses sampled from the populace of Qatar mirrored nearly the entire global population's genomic diversity with nine predominant viral lineages that were sustained by local transmission chains and the emergence of mutations that are likely to have originated in Qatar. We reported an increased number of mutations and deletions in B.1.1.7 and B.1.351 lineages in a short period. These findings raise the imperative need to continue the ongoing genomic surveillance that has been an integral part of the national response to monitor the SARS-CoV-2 profile and re-emergence in Qatar

A population study of clinically actionable genetic variation affecting drug response from the Middle East

Clinical implementation of pharmacogenomics will help in personalizing drug prescriptions and alleviate the personal and financial burden due to inefficacy and adverse reactions to drugs. However, such implementation is lagging in many parts of the world, including the Middle East, mainly due to the lack of data on the distribution of actionable pharmacogenomic variation in these ethnicities. We analyzed 6,045 whole genomes from the Qatari population for the distribution of allele frequencies of 2,629 variants in 1,026 genes known to affect 559 drugs or classes of drugs. We also performed a focused analysis of genotypes or diplotypes of 15 genes affecting 46 drugs, which have guidelines for clinical implementation and predicted their phenotypic impact. The allele frequencies of 1,320 variants in 703 genes affecting 299 drugs or class of drugs were significantly different between the Qatari population and other world populations. On average, Qataris carry 3.6 actionable genotypes/diplotypes, affecting 13 drugs with guidelines for clinical implementation, and 99.5% of the individuals had at least one clinically actionable genotype/diplotype. Increased risk of simvastatin-induced myopathy could be predicted in ~32% of Qataris from the diplotypes of SLCO1B1, which is higher compared to many other populations, while fewer Qataris may need tacrolimus dosage adjustments for achieving immunosuppression based on the CYP3A5 diplotypes compared to other world populations. Distinct distribution of actionable pharmacogenomic variation was also observed among the Qatari subpopulations. Our comprehensive study of the distribution of actionable genetic variation affecting drugs in a Middle Eastern population has potential implications for preemptive pharmacogenomic implementation in the region and beyond. 2022, The Author(s).PVJ is supported by faculty funding from the College of Health & Life Sciences, HBKU. Qatar Biobank and Qatar Genome Program are Research, Development & Innovation's entities within Qatar Foundation for Education, Science and Community Development. Funders had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.Scopu

Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Funder: British Lung Foundation (BLF); doi: https://doi.org/10.13039/501100000351Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272AbstractLung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.</jats:p