The distribution of regions of homozygosity (ROH) among consanguineous populations - implications for a routine genetic counseling service

Background Regions of homozygosity (ROH) increase the risk of recessive disorders, and guidelines recommend reporting of excessive ROH in prenatal testing. However, ROH are common in populations that practice endogamy or consanguinity, and cutoffs for reporting ROH in such populations may not be evidence-based. Methods We reviewed prenatal testing results (based on cytogenetic microarrays) from 2191 pregnancies in the Jewish and non-Jewish populations of Northern Israel and estimated the prevalence of ROH according to self-reported ethnicity and parental relationships. Results The proportion of the genome in ROH, ROH rate, was higher in non-Jews [Mean(SD)=2.91%(3.92%); max=25.54%; N=689] than in Jews [Mean(SD)=0.81%(0.49%); max=3.93%; N=1502]. In the non-Jewsih populations, consanguineous marriages had the highest ROH rates [Mean(SD)=7.14%(4.55%), N=217], followed by endogamous [Mean(SD)=1.13%(1.09%), N=283]) and non-endogamous [Mean(SD)=0.69%(0. 56%), N=189]) marriages. ROH rates were greater than 5%, the ACMG-recommended cutoff, in 149/689 (21.63%) of the non-Jewish samples. Within the Jewish populations, the rates were similar between Ashkenazi, North African, and Middle Eastern Jews, but were higher for six consanguineous unions [Mean(SD)=2.38%(1.23%)] and when spouses belonged to the same sub-population. Conclusions Given the high ROH rates we observed in some subjects, we suggest that assessing the risk for recessive conditions in consanguineous/endogamous populations should be done before the first pregnancy, through genetic counseling and sequencing. Such an approach will: ([1][1]) identify couples who are at risk and counsel them on reproductive options; and ([2][2]) avoid the stress that couples who are not at risk may experience due to a prenatal ROH report. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Ethical Committee of Emek Medical Center (EMC-0073-23), following the Helsinki guidance. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: #ref-1 [2]: #ref-2