Genetic Susceptibility to Infectious Diseases in the Qatari Population

Abstract

Background: Infectious diseases (IDs) account for 8% of deaths annually in Qatar, and therefore, represent a significant challenge for public health. Interestingly, the spread and severity of viral infections vary considerably between individuals and populations. The most recent example is SARS-CoV-2, which ranges from mild/asymptomatic to a severe respiratory syndrome. It has been previously reported that polymorphisms in genes linked to immunity can influence individuals' responses to infections as observed in tuberculosis, influenza, and HIV; however, studies exploring causal host genetic variants in IDs are still limited and dramatically skewed with regard to population inclusion. In fact, the genetic susceptibility to IDs in the Qatari population is largely unknown. Aim: To perform a comprehensive genetic screening to investigate the presence and frequency of variants previously associated with various infections in the Qatari population. Methods: Whole-genome sequencing was previously performed for 18,000 QBB participants using Illumina HiSeq X Ten1 sequencers. The initial data processing and quality assessment of the raw data has also been performed and variant calling files (VCF) were created. We were granted the access to the VCF files of 6,218 sequenced samples. The genetic variant data was then converted to PLINK file format using PLINK-1.9. Standardized quality-assurance and quality control (QA/QC) methods were followed to generate high quality and confidence on both SNPs and sample levels. The final file used for calculating allele frequency contained 6,047 subjects. Additionally, list of infections-related SNPs that were previously reported in the literature and deposited in GWAS catalog was extracted and used to calculate and compare the allelic frequency in the Qatari genomes compared to other populations. Results: The frequency of infections-related SNPs in the Qatari population was significantly lower for most infections. Most variants (78%) showed negative fold change in the Qatari genomes. Only 22% of all variants were more prevalent in Qatari population compared to others. The most significant differences were observed in genes related to TB and HIV (200-940 and 160-710 fold change, respectively). Conclusion: This study reports a lower susceptibility of the Qatari population to IDs in general. Nonetheless, this might also indicate the presence of unknown Qatari-unique variants and hence, highlights the need for further investigation in future GWAS.