Hanna Eileen Marie, Mehawej Cybel, Assy Joelle, Corbani Sandra, Korban Rima, Megarbane Andre, Chouery Eliane
Department of Computer Science and Mathematics, Lebanese American University, Byblos, Lebanon.
Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, Lebanon.
J Mol Diagn. 2025 Mar;27(3):177-183. doi: 10.1016/j.jmoldx.2024.11.008. Epub 2024 Dec 24.
Consanguinity, prevalent in certain populations because of cultural and social factors, significantly increases the risk of genetic autosomal recessive disorders. In Lebanon, consanguineous marriages constitute 35.5% of unions, with first cousin marriages being the most common. This study aims to develop a model to predict consanguinity status using total runs of homozygosity (ROH) size derived from exome sequencing data. In this study, a cohort of 784 Lebanese individuals was analyzed, with consanguinity labels assigned based on pedigree information. ROHs were detected from exome sequencing data using AutoMap. The analysis focused on 521 subjects for whom the consanguinity or nonconsanguinity label was clearly determined, leading to the development of two logistic regression models: one including outliers (accuracy, 91%) and one excluding them (accuracy, 94%). The second model established specific ROH thresholds for categorizing consanguinity: nonconsanguineous [<40.28 megabases (Mb)], uncertain (40.28 to 79.17 Mb), probable consanguinity (79.18 to 118.06 Mb), and consanguineous (>118.06 Mb). This study provides a valuable tool for clinical genetics in populations with high consanguinity rates, offering insights into the genetic risks associated with consanguinity and aiding in the identification and counseling of affected individuals. Moreover, the current findings underline the importance of population-specific thresholds in accurately assessing consanguinity status.
由于文化和社会因素，近亲结婚在某些人群中很普遍，这显著增加了常染色体隐性遗传病的风险。在黎巴嫩，近亲婚姻占婚姻总数的35.5%，其中表亲结婚最为常见。本研究旨在利用外显子组测序数据得出的纯合子连续片段（ROH）总长度建立一个预测近亲结婚状况的模型。在本研究中，对784名黎巴嫩个体组成的队列进行了分析，并根据系谱信息确定了近亲结婚标签。使用AutoMap从外显子组测序数据中检测ROH。分析集中在521名近亲结婚或非近亲结婚标签明确的受试者身上，由此建立了两个逻辑回归模型：一个包括异常值（准确率91%），另一个排除异常值（准确率94%）。第二个模型确定了用于分类近亲结婚状况的特定ROH阈值：非近亲结婚[<40.28兆碱基（Mb）]、不确定（40.28至79.17 Mb）、可能近亲结婚（79.18至118.06 Mb）和近亲结婚（>118.06 Mb）。本研究为近亲结婚率高的人群的临床遗传学提供了一个有价值的工具，有助于深入了解与近亲结婚相关的遗传风险，并帮助识别和咨询受影响个体。此外，目前的研究结果强调了特定人群阈值在准确评估近亲结婚状况方面的重要性。
