Genome-wide association study and meta-analysis of phytosterols identifies a novel locus for serum levels of campesterol.

Sitosterolemia is a rare inherited disorder caused by mutations in the ABCG5/ABCG8 genes. These genes encode proteins involved in the transport of plant sterols. Mutations in these genes lead to decreased excretion of phytosterols, which can accumulate in the body and lead to a variety of health problems, including premature coronary artery disease. We conducted the first genome-wide association study (GWAS) in the Middle East/North Africa population to identify genetic determinants of plant sterol levels in Qatari people. GWAS was performed on serum levels of ß-sitosterol and campesterol using the Metabolon platform from Qatar Biobank (QBB) and genome sequence data provided by Qatar Genome Program. A trans-ancestry meta-analysis of data from our Qatari cohort with summary statistics from a previously published large cohort (9758 subjects) of European ancestry was conducted. Using conditional analysis, we identified two independent single nucleotide polymorphisms associated with ß-sitosterol (rs145164937 and rs4299376), and two others with campesterol (rs7598542 and rs75901165) in the Qatari population in addition to previously reported variants. All of them map to the ABCG5/8 locus except rs75901165 which is located within the Intraflagellar Transport 43 (IFT43) gene. The meta-analysis replicated most of the reported variants, and our study provided significant support for the association of variants in SCARB1 and ABO with sitosterolemia. Evaluation of a polygenic risk score devised from European GWAS data showed moderate performance when applied to QBB (adjusted-R2 = 0.082). These findings provide new insights into the genetic architecture of phytosterol metabolism while showing the importance including under-represented populations in future GWAS studies.

Assessing the genetic burden of familial hypercholesterolemia in a large middle eastern biobank.

BACKGROUND: The genetic architecture underlying Familial Hypercholesterolemia (FH) in Middle Eastern Arabs is yet to be fully described, and approaches to assess this from population-wide biobanks are important for public health planning and personalized medicine. METHODS: We evaluate the pilot phase cohort (n = 6,140 adults) of the Qatar Biobank (QBB) for FH using the Dutch Lipid Clinic Network (DLCN) criteria, followed by an in-depth characterization of all genetic alleles in known dominant (LDLR, APOB, and PCSK9) and recessive (LDLRAP1, ABCG5, ABCG8, and LIPA) FH-causing genes derived from whole-genome sequencing (WGS). We also investigate the utility of a globally established 12-SNP polygenic risk score to predict FH individuals in this cohort with Arab ancestry. RESULTS: Using DLCN criteria, we identify eight (0.1%) 'definite', 41 (0.7%) 'probable' and 334 (5.4%) 'possible' FH individuals, estimating a prevalence of 'definite or probable' FH in the Qatari cohort of ~ 1:125. We identify ten previously known pathogenic single-nucleotide variants (SNVs) and 14 putatively novel SNVs, as well as one novel copy number variant in PCSK9. Further, despite the modest sample size, we identify one homozygote for a known pathogenic variant (ABCG8, p. Gly574Arg, global MAF = 4.49E-05) associated with Sitosterolemia 2. Finally, calculation of polygenic risk scores found that individuals with 'definite or probable' FH have a significantly higher LDL-C SNP score than 'unlikely' individuals (p = 0.0003), demonstrating its utility in Arab populations. CONCLUSION: We design and implement a standardized approach to phenotyping a population biobank for FH risk followed by systematically identifying known variants and assessing putative novel variants contributing to FH burden in Qatar. Our results motivate similar studies in population-level biobanks - especially those with globally under-represented ancestries - and highlight the importance of genetic screening programs for early detection and management of individuals with high FH risk in health systems.

Assessment of Qatar's Health Care Community Call Center Efficacy in Addressing COVID-19 Pandemic Health Care Challenges: Cross-Sectional Study.

BACKGROUND: The global COVID-19 pandemic caused by SARS-CoV-2 created many unprecedented challenges for health care organizations worldwide, placing a great deal of strain on the health care systems, especially access to health care services. To address these challenges, Qatar established a centralized digital platform as a community call center, initially offering digital consultations via its hotline (number: 16000) and later expanding to include a COVID-19 vaccination hotline (number: 7077) for mass immunization. OBJECTIVE: This study aims to comprehensively examine the community call center's operations and their significant role during the COVID-19 pandemic. METHODS: Retrospective data were collected from the Health Information and Technology Department of the Primary Health Care Corporation, Qatar, from March 29, 2020, to January 27, 2022. Data analysis for the hotline (number: 16000) focused on telephone and video call volumes, call response rates, abandonment rates, and call classification. In addition, data from the COVID-19 vaccination hotline (number: 7077) were analyzed for call volumes, call response rates, abandonment rates, appointment booking rates, confirmations, rescheduling, and cancellations. RESULTS: The hotline (number: 16000) received a substantial total of 429,212 calls, with 284,849 (66.37%) calls effectively answered. The average number of calls received per day during the study period was 640.61 (SD 470.53), and the average number of calls answered per day was 425.14 (SD 206.64). Notably, of the total 128,468 consultations, video consultations were conducted for 3810 (2.96%). Among the diverse call categories, diabetes mellitus (6284/84,299, 7.45%), prescriptions and medications (4709/84,299, 5.59%), hypertension (3874/84,299, 4.6%), vitamin D-related issues (3770/84,299, 4.47%), upper respiratory tract infections (2690/84,299, 3.19%), and COVID-19-related inquiries (2590/84,299, 3.07%) were most frequently addressed. For the COVID-19 vaccination hotline (number: 7077), an impressive total of 1,512,354 calls were received, with a 58.27% (n=881,305) call response rate. The average number of calls per day during the study period was 3828.74 (SD 2931.94), and the average number of calls answered per day was 2231.15 (SD 1496.02). Appointment booking accounted for 26.37% (265,721/1,007,596), appointment confirmation accounted for 10.24% (103,136/1,007,596), rescheduling accounted for 7.95% (80,124/1,007,596), and cancellations accounted for 1.6% (16,128/1,007,596) of the calls. CONCLUSIONS: The findings of this research highlight the crucial significance of the community call center hotline (number: 16000) and the COVID-19 vaccination hotline (number: 7077) in effectively addressing the multifaceted challenges posed by the global COVID-19 pandemic. In Qatar, the community call center emerged as an indispensable and accessible centralized resource, facilitating streamlined digital consultations and vaccination appointments. The impressive call response rate highlights its operational efficiency, adeptly managing a diverse range of health-related issues. This study emphasizes the critical role of community call centers in health care emergency response, signaling their potential as invaluable assets for future preparedness and effective mitigation strategies during similar public health crises.

Pharmacogenomics Variability of Lipid-Lowering Therapies in Familial Hypercholesterolemia.

The exponential expansion of genomic data coupled with the lack of appropriate clinical categorization of the variants is posing a major challenge to conventional medications for many common and rare diseases. To narrow this gap and achieve the goals of personalized medicine, a collaborative effort should be made to characterize the genomic variants functionally and clinically with a massive global genomic sequencing of "healthy" subjects from several ethnicities. Familial-based clustered diseases with homogenous genetic backgrounds are amongst the most beneficial tools to help address this challenge. This review will discuss the diagnosis, management, and clinical monitoring of familial hypercholesterolemia patients from a wide angle to cover both the genetic mutations underlying the phenotype, and the pharmacogenomic traits unveiled by the conventional and novel therapeutic approaches. Achieving a drug-related interactive genomic map will potentially benefit populations at risk across the globe who suffer from dyslipidemia.