Laboratory MAP5 UMR CNRS 8145 Paris City University, Paris, France.
Department of Neurology, Henri Mondor University Hospital, APHP, Crteil, France.
PLoS One. 2023 Aug 10;18(8):e0288958. doi: 10.1371/journal.pone.0288958. eCollection 2023.
In genetic diseases with variable age of onset, an accurate estimation of the survival function for the mutation carriers and also modifying factors effects estimations are important for the management of asymptomatic gene carriers across life. Among the modifying factors, the gender of the parent transmitting the mutation (i.e. the parent-of-origin effect) has been shown to have a significant effect on survival curve estimation on transthyretin familial amyloid polyneuropathy (ATTRv) families. However, as most genotypes are unknown, the parent-of-origin must be calculated through a probability estimated from the pedigree. We propose in this article to extend the method providing mutation carrier survival estimates in order to estimate the parent-of-origin effect. The method is both validated on simulated data and applied to familly samples with ATTRv.
在发病年龄存在变异的遗传性疾病中，准确估计突变携带者的生存函数以及对修饰因子效应的估计，对于在个体一生中管理无症状基因携带者至关重要。在这些修饰因子中，已证明父源传递突变的性别（即亲源性效应）对转甲状腺素蛋白家族性淀粉样多发性神经病（ATTRv）家族的生存曲线估计有重大影响。然而，由于大多数基因型未知，亲源性必须通过从系谱中估计的概率来计算。本文提出了扩展提供突变携带者生存估计的方法，以估计亲源性效应。该方法在模拟数据上进行了验证，并应用于具有 ATTRv 的家族样本。
