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首页> 外文期刊>Human Heredity >Estimating disease risk associated with mutated genes in family-based designs.
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Estimating disease risk associated with mutated genes in family-based designs.

机译：在基于家庭的设计中估算与突变基因相关的疾病风险。

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摘要

OBJECTIVE: Many clinical decisions require accurate estimates of disease risk associated with inherited gene mutations. While several family-based designs have been proposed, their relative advantages remain unclear. METHODS: We considered four commonly-used family-based designs and evaluated their performance in terms of accuracy and efficiency under several genetic models via simulation studies. We also derived and assessed several ascertainment-corrected likelihood methods for analyzing the simulated data and real data from 12 HNPCC pedigrees from Newfoundland. RESULTS: We found that the design efficiency depends on the question of interest: the clinic-based family design with random probands yields the most efficient estimate of genetic relative risks, whereas the population-based family design with mutation carrier probands provides the most efficient penetrance estimates. For a particular question, an ascertainment correction seems possible using regular likelihood methods but the presence of genetic heterogeneity due to a strong second gene effect can lead to some bias in the risk estimation. CONCLUSIONS: This work gives a general methodological framework for analyzing family-based designs in gene characterization studies and provides more rationale for the choice of an efficient design and an appropriate likelihood method to estimate the risk associated with an inherited gene mutation.
机译：目的：许多临床决策需要准确估计与遗传基因突变相关的疾病风险。虽然已经提出了几种基于家庭的设计，但是它们的相对优势仍然不清楚。方法：我们考虑了四种常用的基于家庭的设计，并通过模拟研究在几种遗传模型下评估了它们在准确性和效率方面的表现。我们还推导并评估了几种确定性校正的似然方法，用于分析来自纽芬兰的12个HNPCC家谱的模拟数据和真实数据。结果：我们发现设计效率取决于感兴趣的问题：随机先证者的基于临床的家庭设计产生了相对遗传风险的最有效估计，而突变携带者先证的基于人口的家庭设计提供了最有效的渗透率估计。对于一个特定的问题，使用常规似然方法确定校正似乎是可能的，但是由于强烈的第二基因效应而导致的遗传异质性的存在可能导致风险估计上的某些偏差。结论：这项工作为在基因表征研究中分析基于家族的设计提供了一个通用的方法学框架，并为选择有效设计和合理的可能性方法提供了更多理论依据，以估算与遗传基因突变相关的风险。

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