Burden of Mendelian disorders in a large Middle Eastern biobank

Genome sequencing of large biobanks from under-represented ancestries provides a valuable resource for the interrogation of Mendelian disease burden at world population level, complementing small-scale familial studies. Here, we interrogate 6045 whole genomes from Qatar—a Middle Eastern population with high consanguinity and understudied mutational burden—enrolled at the national Biobank and phenotyped for 58 clinically-relevant quantitative traits. We examine a curated set of 2648 Mendelian genes from 20 panels, annotating known and novel pathogenic variants and assessing their penetrance and impact on the measured traits. We find that 62.5