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

Genetic Epidemiology of Hearing Loss in the 22 Arab Countries: A Systematic Review

Hearing loss (HL) is a heterogeneous condition that causes partial or complete hearing impairment. Hundreds of variants in more than 60 genes have been reported to be associated with Hereditary HL (HHL). The HHL prevalence is thought to be high in the Arab population; however, the genetic epidemiology of HHL among Arab populations is understudied. This study aimed to systematically analyze the genetic epidemiology of HHL in Arab countries. We searched four literature databases (PubMed, Scopus, Science Direct, and Web of Science) from the time of inception until January 2019 using broad search terms to capture all the reported epidemiological and genetic data related to Arab patients with HHL. A total of 2,600 citations were obtained; 96 studies met our inclusion criteria. Our search strategy yielded 121,276 individuals who were tested for HL over 52 years (1966-2018), of whom 8,099 were clinically diagnosed with HL and belonged to 16 Arab countries. A total of 5,394 patients and 61 families with HHL were genotyped, of whom 336 patients and 6 families carried 104 variants in 44 genes and were from 17/22 Arab countries. Of these variants, 72 (in 41 genes) were distinctive to Arab patients. Arab patients manifested distinctive clinical phenotypes. The incidence of HHL in the captured studies ranged from 1.20 to 18 per 1,000 births per year, and the prevalence was the highest in Iraq (76.3%) and the lowest in Jordan (1.5%). This is the first systematic review to capture the prevalence and spectrum of variants associated with HHL in an Arab population. There appears to be a distinctive clinical picture for Arab patients with HHL, and the range and distribution of variants among Arab patients differ from those noted in other affected ethnic groups.Qatar National Librar

Association of genetic variants with colorectal cancer in the extended MENA region: A systematic review

Colorectal cancer (CRC) is the third most common cancer worldwide and the third leading cause of cancer-related death. It is a heterogeneous disease that develops through different genetic and epigenetic mechanisms. To date, no comprehensive systematic review study has been performed on the extended MENA (eMENA) region to investigate the genetic risk factors for familial and sporadic CRC. This study aimed to systematically analyze the genetic variations that are significantly associated with CRC in the eMENA region. We searched four literature databases (PubMed, Scopus, Science Direct, and Web of Science) from the time of inception until May 2019 using broad search terms to obtain all the reported genetic data related to the eMENA patients with CRC. Variants with OR>1 that are associated with CRC were captured. A total of 1,200 studies were obtained from our search method; 27 studies met the inclusion criteria for our systematic review. A total of 8,230 CRC patients and 7,611 controls were captured. Of these, 1,941 patients were found to carry 46 variants in 33 different genes that are distributed throughout nine eMENA countries. Interestingly, 19 variants were unique to the CRC patients in the eMENA region (rs63750042, rs267608121, rs267608119, rs2069426, rs63750875, rs16940372, rs4775053, rs4775072, rs9652472, rs35509282, rs2985, rs371608994, rs6983267, rs419598, rs2222722). This is the first systematic review to capture the spectrum of variants that are significantly associated with CRC in the eMENA region. There seems to be a distinctive clinical picture in the eMENA patients with CRC, and the range and distribution of variants among patients from the eMENA region are different from those noted in other affected ethnic groups

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

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