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

Journal of Human Genetics volume 70, pages 99–104 (2025)Cite this article

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Abstract

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. 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. 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-Jewish 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. 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) identify couples who are at risk and counsel them on reproductive options; and (2) avoid the stress that couples who are not at risk may experience due to a prenatal ROH report.

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Data availability

The data that support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

We want to express our gratitude to Professor Joel Zlotogora for his valuable notes and suggestions.

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Authors and Affiliations

  1. Genetics Institute, Emek Medical Center, Afula, Israel

    Chen Gafni-Amsalem, Nasim Warwar, Morad Khayat, Yasmin Tatour, Olfat Abuleil-Zuabi & Stavit A. Shalev

  2. Research Authority, Emek Medical Center, Afula, Israel

    Salvatore Campisi-Pinto

  3. Faculty of Medicine, Braun School of Public Health, Hebrew University of Jerusalem, Ein Kerem, Jerusalem, Israel

    Shai Carmi

  4. Technion Israel Institute of Technology The Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel

    Stavit A. Shalev

Authors
  1. Chen Gafni-Amsalem
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  2. Nasim Warwar
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  5. Olfat Abuleil-Zuabi
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  7. Shai Carmi
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  8. Stavit A. Shalev
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Contributions

Conceptualization: CGA, NV, MK, YT, and SAS; formal analysis: CGA, and SCP; methodology: CGA, NV, YT, OAZ, SC, and SAS; investigating: CGA, NV, YT, SC, and SAS; project administration: CGA, NV, MK, YT, OAZ, and SAS; supervision: SAS; validation: CGA, SC, OAZ, NV, MC, and SAS; writing—original draft: CGA; writing, review, and editing: CGA, SC, and SAS.

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Correspondence to Chen Gafni-Amsalem.

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The authors declare no competing interests.

Ethics approval and consent to participate

The study protocol was approved by the ethical committee of the Emek Medical Center, Afula, following the Helsinki Declaration. Research number EMC-0073-23. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. This study used anonymized retrospective data, therefore consent forms were not required.

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Gafni-Amsalem, C., Warwar, N., Khayat, M. et al. The distribution of regions of homozygosity (ROH) among consanguineous populations—implications for a routine genetic counseling service. J Hum Genet 70, 99–104 (2025). https://doi.org/10.1038/s10038-024-01303-z

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