25 November 2020
Novel genetic variations linked to metabolic disorders in Arabs
Published online 15 September 2020
A comparison highlights differences in genetic risk loci for metabolic diseases between Arab and European populations.
Genome-wide association studies (GWAS) have transformed the way scientists identify associations between variations in genes and disease susceptibility. However, despite the fact that the Arab population has a high prevalence of metabolic disease, most global GWAS conducted to date have used data from predominantly European populations to identify genetic associations with metabolic disorders. This means that the results are missing genetic variants that are specific to different ethnic populations.
“Metabolic disorders, such as diabetes, have reached ‘slow-moving pandemic’ status, thanks in large part to the global shift towards sedentary lifestyles and urbanisation,” says Thangavel Thanaraj at the Dasman Diabetes Institute in Kuwait. “To handle this considerable health challenge, we must first understand whether the genetic loci that have been linked to metabolic traits are transferable to all population groups. Few studies have attempted this for the Arab population.”
Thanaraj, Fahd Al-Mulla and Prashantha Hebbar, with other scientists from the Middle East, Finland and Canada, conducted a meta-analysis that compared published GWAS data from two Kuwaiti Arab cohorts to data from the global 1000 Genomes Project. They searched for genetic associations (variations in genes and pathways) linked to 13 metabolic traits. They identified 821 variants from 251 genes. 95% of the these genes were already linked to metabolic disorders. The researchers identified 53 novel variant association signals specific to the Arab population in the remaining genes.
“We expected to find new variants,” says Hebbar. “Regional cultural practices, including consanguinity (marriage within families) and living in isolation in tribes, has led to increased inbreeding and considerable, often damaging, alterations to the gene pool.”
These findings highlight the need for sharing data and resources to conduct extensive, population-specific research into genetic risk factors for metabolic disorders. Further, drug targets generated by global GWAS must be checked with a broad range of populations to determine the best therapies for each ethnic group.
“Our study provides valuable insights into the causal signatures for metabolic disorders in the Middle East, and takes us a step closer to personalized medicine initiatives,” says Al-Mulla.
“This study is one of the few to highlight the unique genetic profiles of the Arab population,” says molecular cell biologist Rana Dajani at Hashemite University in Jordan, who was not involved in the study. “These critical results will help ensure delivery of more efficient health support, not only for the Arab nations but for migrants of Arab descent who live across the world.”
Hebbar, P. et al. Genome-wide landscape establishes novel association signals for metabolic traits in the Arab population. Hum. Genet. https://doi.org/10.1007/s00439-020-02222-7 (2020).