Premarital genomic screening in Arab populations of the Middle East

Abstract

Premarital genomic screening can help curb the burden of rare recessive disorders in populations with high rates of consanguineous marriages. Arab populations of the Middle East have a unique genetic blend characterized by founder mutations due to historical bottlenecks, and diverse allelic series shaped by a long history of migrations and intermixing. The risk of homozygous pathogenic variants, which can lead to recessive genetic disorders, is elevated because of the high prevalence of consanguineous marriages, particularly unions between first cousins, culturally rooted in this region¹. As a result, the cumulative incidence of rare recessive disorders is expected to be higher in Arab populations compared to others, often leading to chronic, severe and life-limiting conditions, such as hemoglobinopathies, spinal muscular atrophy, congenital malformations and metabolic disorders². This places an immense emotional and financial strain on affected families and healthcare systems across the region.

Premarital genomic screening presents a promising solution to mitigate this growing burden. By identifying carrier couples before marriage (particularly those who may unknowingly harbor the same deleterious variants), this approach provides critical information that enables informed reproductive decisions and could substantially reduce the incidence of genetic disorders and their associated burden across the region. Couples identified as carriers can seek genetic counseling to understand the implications of their results and to explore a range of options, including in vitro fertilization and pre-implantation genetic diagnosis or alternative family planning strategies. Regions that have successfully implemented screening programs have seen a marked decline in the incidence of recessive genetic conditions, further demonstrating their efficacy^3,4,5. Growing evidence from the region suggests that carrier screening offers a cost-effective preventive strategy relative to postnatal treatment or other management alternatives⁶.