Whole-Genome Sequencing in Galicia Reveals Male-Biased Pre-Islamic North African Ancestry, Subtle Population Structure, and Microgeographic Patterns of Disease Risk

Abstract

Galicia, at the westernmost edge of Europe, exhibits distinctive genetic traits compared to other Iberian populations. We present the first whole-genome sequencing (WGS) study of a Galician population (GALOMICS; n = 91; 17.2 M variants; https://galomics.genpob.eu), analyzed alongside WGS data from other Spanish and continental populations (n = 1078). Contrary to recent claims of extreme genetic stratification, Galicia's structure reflects broader Iberian patterns, characterized by one major genetic cluster and four minor, localized ones. Analyses of the Spanish National DNA Bank (NDNAB; n = 453) confirm this pattern, with three Galician clusters, one clearly predominant. Phylogenetic analysis places Galician clusters on terminal, recently diverged branches, challenging earlier models suggesting ancient separation. Slightly elevated homozygosity, driven by the Porto do Son cluster, suggests mild regional inbreeding. A notable North African/Middle Eastern ancestry component (13.5%–16.5%) appears, likely introduced via trans-Mediterranean contact ca. 620–670 ce, predating the Islamic conquest of 711 ce, with a subtle south-to-north gradient and a male-biased signal (Y-DNA: 21.2%; mtDNA: 1.1%). This calls for reexamining assumptions about Islamic-era ancestry. Finally, Polygenic Risk Scores for common diseases (e.g., cancer, Alzheimer's disease, diabetes, autism) show geographic variability aligned with genetic substructure, highlighting the relevance of regional genomics to public health policy.