Exploring the human genomic landscape: patterns of common homozygosity regions in a large middle eastern cohort

Abstract

Abstract Regions of Homozygosity (ROH) typically reflect normal demographic history of a human population, but may also relate to cryptic consanguinity, and, additionally, have been associated with specific medical conditions. The objective of this study was to investigate the location, size, and prevalence of common ROH segments in a Middle Eastern cohort. This retrospective study included 13 483 samples collected from all Chromosomal Microarray analyses (CMA) performed using Single Nucleotide Polymorphism (SNP) arrays at the genetic clinical laboratory of Rabin Medical Center between 2017–2023 (primary data set). An additional replication cohort including 100 842 samples from another SNP array platform, obtained from Maccabi Health Organization, was analyzed. Common ROH locations were defined as those ROH locations involving 1% or more of the samples. A total of 66 710 ROH segments, involving 13 035 samples (96.7%) were identified in the primary data set. Of the 4069 cytogenetic ROH locations, 68 were identified as common. The prevalence of non-common ROH was relatively high in affected individuals, and for acrocentric chromosomes, chromosomes associated with common trisomies, and non-imprinted chromosomes. In addition, differences in common ROH locations were observed between the primary and the replication cohorts. Our findings highlight the need for population-specific guidelines in determining ROH reporting cutoffs, considering factors such as population-specific prevalence and testing platform differences. Future research with larger, varied cohorts is essential to advance understanding of ROH’s associations with medical conditions and to improve clinical practices accordingly.