Nature Genetics study creates a new resource to unravel genome complexity and advance precision medicine for Arab populations
Doha, Qatar: Researchers at Sidra Medicine, a member of Qatar Foundation, have created the Middle East’s first population-scale atlas showing how genetic variation regulates gene activity in blood and tracing its effects to clinical traits.
Published in Nature Genetics, the study, titled “A catalogue of transcriptome genetic regulation in a consanguineous Middle Eastern biobank”, provides a new resource to advance precision medicine and addresses a major gap in global genomics and advances precision medicine by enabling more precise genetic diagnosis and disease-risk prediction, while supporting the discovery of new biomarkers and therapeutic targets.
Prof. Younes Mokrab, Principal Investigator in Genome and Biomedicine Informatics and Director of the Neuroscience Research Program
Mapping how genes influence health and disease
Despite major genome sequencing efforts worldwide, little is known about what most genetic variants do and how they influence health and disease. This gap is even greater for Arab and Middle Eastern populations, where genetic diversity and the broad effects of high consanguinity remain understudied.
Led by Prof. Younes Mokrab, Principal Investigator in Genome and Biomedicine Informatics and Director of the Neuroscience Research Program, with Dr. Haroon Naeem, Staff Scientist as First Author, the research team drew on data from nearly 2,000 Qatar Biobank participants, combining whole-genome sequencing, whole-blood transcriptomics and detailed clinical information.
The team traced, across the entire genome, how variation at the DNA level influences gene regulation, and how these changes connect to health and diseases. Moving beyond conventional associations, they applied advanced computational techniques uncovering nearly 30,000 “causal” effects that control how the genome is transcribed and linking them to 20 clinical traits and disease pathways, including those related to key immune and metabolic function.
Prof. Younes Mokrab said: “The genome is the body’s genetic blueprint, while the blood transcriptome shows that blueprint in action. Using a population-level cohort from QBB, we brought these layers together with clinical information. Leveraging advanced analytics, we moved beyond genetic associations to uncover causal effects on gene regulation and health at a genome-wide scale. This is particularly important for Middle Eastern populations, where there is still so much to uncover about their genetic diversity and its biological and clinical significance.”
Dr. Haroon Naeem, Staff Scientist
Impact of consanguinity on gene regulation
The study also revealed the less understood effect of consanguinity on gene activity. Consanguinity increases the chance of inheriting two copies of the same genetic variant, a phenomenon best known for its role in rare genetic diseases. The researchers showed that inheriting two copies of certain regulatory variants can also lead to unusually high or low activity of specific genes, extending the biological impact of consanguinity beyond variants that directly alter proteins.
First author Dr. Haroon Naeem, Staff Scientist in the Genome and Biomedicine Informatics Laboratory, said: “We leveraged the high levels of consanguinity in our study cohort to gain novel insights into the impact of inbreeding on gene regulation, revealing effects that extend beyond its established role in recessive genetic disease.”
Advancing genomic medicine from diagnosis to discovery
The research represents a significant milestone in improving the interpretation of genomic test results and increasing the yield of genetic diagnosis through better annotation of non-coding variants. Also, it enables the development of ancestry-aware, functionally-informed polygenic scores for better assessment of risk to complex diseases and more successful clinical trials. By linking known variants to their target genes, the findings will also prioritize new targets for functional investigation and the validation of biomarkers and therapeutic targets grounded in disease biology.
Prof. Khalid Fakhro, Chief Research Officer at Sidra Medicine, said: “Precision medicine relies heavily on population-matched reference databases, and this study builds exactly that for RNA data, to complement the extensive DNA resources we have built for Qatar and the Middle East over the years. Building such resources requires deep expertise and world class core facilities, and creates a foundation for personalized healthcare for our populations.”
Prof. Khalid Fakhro, Chief Research Officer at Sidra Medicine
Building a resource for AI and future research
The study demonstrates the power of integrating national genomic resources with multi-omic research to advance biological and clinical discovery in emerging target populations.
The dataset generated in the study provides a rich multimodal resource that is being further enriched with additional layers of omics data from Qatar Biobank and disease-focused cohorts at Sidra Medicine, creating a foundation for next-generation AI and machine learning models to improve disease prediction and identify potential treatments.
Prof. Mokrab concluded: “The value of this resource is ultimately in what it enables: a stronger biological basis to resolve difficult genetic diagnoses, build more relevant risk models for diverse populations, and prioritize promising findings for functional validation and therapeutic development. Looking ahead, combining national resources such as Qatar Biobank with disease cohorts at Sidra Medicine, enriched with multiple layers of data, will create a powerful foundation for AI-driven discovery, translating our region’s unique genetic makeup into better health for our patients.”
The study was supported by Sidra Medicine and the Qatar National Research Fund, leveraging data and samples from Qatar Biobank and the Qatar Genome Program, now part of the Qatar Precision Health Institute. The full research paper is available in Nature Genetics and can be accessed here: https://www.nature.com/articles/s41588-026-02785-7
