Genome-wide analysis of runs of homozygosity in Pakistani controls with no history of speech or language-related developmental phenotypes.

Background: Runs of homozygosity (ROHs) analysis of controls provide a convenient resource to minimize the association of false positive results of disease-associated ROHs and genetic variants for simple and complex disorders in individuals from the same population. Evidence for the value of ROHs to speech or language-related traits is restricted due to the absence of population-matched behaviourally defined controls and limited family-based studies.

Aim: This study aims to identify common ROHs in the Pakistani population, focussing on the total length and frequency of ROHs of variable sizes, shared ROHs, and their genomic distribution.

Subjects and methods: We performed homozygosity analysis (in PLINK) of 86 individuals (39 males, 47 females) with no history of speech or language-related phenotypes (controls) who had been genotyped with the Illumina Infinium QC Array-24.

Results: ROHs of 1-<4 megabases (Mb) were frequent in unrelated individuals. We observed ROHs over 20 Mb among six individuals. Over 30 percent of the identified ROHs were shared among several individuals, indicating consanguinity's effect on the Pakistani population.

Conclusion: Our findings serve as a foundation for family-based genetic studies of consanguineous families with speech or language-related disorders to ultimately narrow the homozygosity regions of interest to identify pathogenic variants.