The genetic landscape of autism spectrum disorder in the Middle Eastern population.

Introduction: Autism spectrum disorder (ASD) is characterized by aberrations in social interaction and communication associated with repetitive behaviors and interests, with strong clinical heterogeneity. Genetic factors play an important role in ASD, but about 75% of ASD cases have an undetermined genetic risk. Methods: We extensively investigated an ASD cohort made of 102 families from the Middle Eastern population of Qatar. First, we investigated the copy number variations (CNV) contribution using genome-wide SNP arrays. Next, we employed Next Generation Sequencing (NGS) to identify de novo or inherited variants contributing to the ASD etiology and its associated comorbid conditions in families with complete trios (affected child and the parents). Results: Our analysis revealed 16 CNV regions located in genomic regions implicated in ASD. The analysis of the 88 ASD cases identified 41 genes in 39 ASD subjects with de novo (n = 24) or inherited variants (n = 22). We identified three novel de novo variants in new candidate genes for ASD (DTX4, ARMC6, and B3GNT3). Also, we have identified 15 de novo variants in genes that were previously implicated in ASD or related neurodevelopmental disorders (PHF21A, WASF1, TCF20, DEAF1, MED13, CREBBP, KDM6B, SMURF1, ADNP, CACNA1G, MYT1L, KIF13B, GRIA2, CHM, and KCNK9). Additionally, we defined eight novel recessive variants (RYR2, DNAH3, TSPYL2, UPF3B KDM5C, LYST, and WNK3), four of which were X-linked. Conclusion: Despite the ASD multifactorial etiology that hinders ASD genetic risk discovery, the number of identified novel or known putative ASD genetic variants was appreciable. Nevertheless, this study represents the first comprehensive characterization of ASD genetic risk in Qatar's Middle Eastern population.

Comparison of demographic, clinical and laboratory characteristics between first and second COVID-19 waves in a secondary care hospital in Qatar: a retrospective study.

OBJECTIVE: To compare the patient profile and outcomes in Qatar during the first and second waves of the COVID-19 pandemic. SETTING: A retrospective observational study was conducted comparing the demographic, clinical and laboratory characteristics of patients with COVID-19 infection admitted to a secondary care hospital, during the first and second waves of the pandemic. PARTICIPANTS: 1039 patients from the first wave and 991 from the second wave who had pneumonia on chest X-ray and had a confirmed SARS-CoV-2 infection by a real-time PCR test of a nasopharyngeal swab were included. Patients with a normal chest X-ray and those who had a negative PCR test despite a positive COVID-19 antigen test were excluded. OUTCOME: Length of stay, need for mechanical ventilation, final disposition and mortality were the key outcomes studied RESULTS: Influenza like symptoms (18.5% in the first wave vs 36.1% in the second wave, p 0.001), cough (79.2% vs 87%, p<0.001) and dyspnoea (27.5% vs 38% p<0.001) were more common in the second wave. Second wave patients had significantly higher respiratory rate, lower peripheral oxygen saturation, needed more supplemental oxygen and had higher incidence of pulmonary embolism. More patients received hydroxychloroquine and antibiotics during the first wave and more received steroids, antivirals and interleukin-1 antagonist during the second wave. The second wave had a shorter length of stay (14.58±7.75 vs 12.61±6.16, p<0.001) and more patients were discharged home (22% vs 10%, p<0.001). CONCLUSIONS: Patients who presented during the second wave of COVID-19 pandemic appeared to be more ill clinically and based on their laboratory parameters. They required shorter hospitalisation and were more likely to be discharged home. This could represent greater expertise in handling such patients that was acquired during the first wave as well as use of more appropriate and combination therapies during the second wave.

Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traits.

Clinical laboratory tests play a pivotal role in medical decision making, but little is known about their genetic variability between populations. We report a genome-wide association study with 45 clinically relevant traits from the population of Qatar using a whole genome sequencing approach in a discovery set of 6218 individuals and replication in 7768 subjects. Trait heritability is more similar between Qatari and European populations (r = 0.81) than with Africans (r = 0.44). We identify 281 distinct variant-trait-associations at genome wide significance that replicate known associations. Allele frequencies for replicated loci show higher correlations with European (r = 0.94) than with African (r = 0.85) or Japanese (r = 0.80) populations. We find differences in linkage disequilibrium patterns and in effect sizes of the replicated loci compared to previous reports. We also report 17 novel and Qatari-predominate signals providing insights into the biological pathways regulating these traits. We observe that European-derived polygenic scores (PGS) have reduced predictive performance in the Qatari population which could have implications for the translation of PGS between populations and their future application in precision medicine.