Patterns of population structure and genetic variation within the Saudi Arabian population

Abstract

1 bioRxiv preprint doi: https://doi.org/10.1101/2025.01.10.632500; this version posted May 6, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 Both the demographic history and cultural practices influence the pattern of genetic variation, sometimes in opposing manners. For Saudi Arabians, being situated at the hub connecting multiple continents is expected to increase heterogeneity and diversity due to cross-continental migrations. On the other hand, cultural practices such as endogamy to promote social stability may have also promoted regional isolations and reduced heterogeneity. To better understand the genomic impact of these potentially opposing forces, we genotyped and sequenced 3,352 and 302 individuals, respectively, from Saudi Arabians to study their population structure and admixture history, and patterns of genetic variation. We identified twelve genetic sub-clusters that correlated with geographical regions, differentiated by distinct components of ancestry based on comparisons to modern and ancient DNA references. These sub-clusters also showed variation across ranges of the genome covered in runs of homozygosity, reflecting potential differences in kinship or marital practices, as well as differences in population size changes over time. Using 25,488,981 variants found in whole genome sequencing, we found that the Saudi do not show the depletion of rare alleles typically observed in isolated populations, though they do show the expected pattern of enrichment of alleles bioinformatically annotated as deleterious when compared to Africans/African Americans and Non-Finnish Europeans from gnomAD. Saudi sub-clusters with greater inbreeding and lower effective population sizes showed greater enrichment of deleterious alleles as well. Taken together, our results suggest that Saudi’s history and culture impact its pattern of genetic variation and potentially to the population health. We also made available the allele frequency estimates of alleles discovered in our samples so to start a foundation on which to interpret medical- and pharmaco- genomic findings from these populations. 2 bioRxiv preprint doi: https://doi.org/10.1101/2025.01.10.632500; this version posted May 6, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 47