NEW YORK – Members of the Qatar Genome Programme (QGP) team have identified immune-related gene expression differences in individuals participating in the population sequencing study, as well as regulatory features that are shared with, and distinct from, those found in other populations so far.
In a Friday presentation at the American Society of Human Genetics virtual conference, Haroon Naeem, a staff scientist in medical and population genomics at Sidra Medicine outlined findings from the transcriptome sequencing arm of the QGP study, which is attempting to understand the genetic diversity of individuals who have made their way to the small peninsular country in the Persian Gulf.
Investigators behind the broader QGP population project have already done whole-genome sequencing on more than 6,200 phenotyped adults enrolled in the Qatar Biobank, he noted, generating Illumina paired-end sequences to an average depth of 30-fold coverage per genome.
"The Qatar Genome Programme has set up a large sequencing cohort in Qatar, which is located in a region of historic migration and civilization," Naeem explained, adding that the QGP cohort is expected to provide "context to the wider Arab and Middle Eastern populations [that are] still largely missing from public databases."
Population structure analyses done with data from QGP and the 1000 Genomes Project pointed to at least five main genetic clusters in Qatar, each made up of individuals with different proportions of ancestral sequences related to those in Arab, European, African, South Asian, and Asian reference populations, he reported.
After bringing in additional population clues from the Human Genome Diversity Project, the researchers found that more than three-quarters of the samples considered broadly fit into the Peninsular Arab, General Arab, or West Eurasian/Persian groups.
But the team also wanted to get a look at the potential functional effects of the genetic variation in the Qatari population as well — from blood gene expression differences to distinct regulatory features and their pathway effects.
Using peripheral whole blood samples collected from QGP participants, he and his colleagues did RNA sequencing on 2,127 of these individuals. After quality control, sequence filtering, and read trimming steps they were left with transcriptome sequences for 1,882 of those samples, which were analyzed alongside the human reference genome as well as genomic, clinical, lifestyle, and other phenotypic clues collected for QGP.
On the expression side, the team primarily saw differences affecting genes from immune-related pathways, Naeem reported, including an antigen presentation pathway, a pathway implicated in allograft rejection signaling, T cell signaling pathways, and PD-1/PD-L1 immune checkpoint pathways.
"[W]e discovered a high level of transcriptomic diversity in the Qatari population, highlighting differential activity of immune related pathways and suggesting ancestral differences in disease risk and susceptibility to infection," Naeem and co-authors from Sidra Medicine, Hamad Bin Khalifa University, and Stanford University proposed in the abstract accompanying the conference presentation.
The researchers went on to catalog and begin characterizing expression quantitative trait loci (QTL) and transcript splicing QTLs within and across the genetically clustered groups in Qatar, comparing the eQTL and SQTL patterns to those described in past studies of other populations around the world.
"[T]he results from this study contribute towards building a highly-sought population-matched reference dataset for the under-studied populations of the Middle East," the authors wrote, "allowing the interpretation of causal effects of genetic variants underlying health and disease worldwide."