标题: | 加入共变數于三元体资料分析以估计疾病基因位置 Incorporating Covariates into Linkage-Disequilibrium Mapping Using the Case-Parent Trio Design |
作者: | 李昱纬 Lee, Yu-Wei 邱燕枫 Chiu, Yen-Feng 统计学研究所 |
关键字: | 多点检定;连锁不平衡;三元体资料;连续型变数;有母数方法;无母数方法;Multipoint;Likage disequilibrium;Case-parent trio design;Covariates;Parametric approaches;Nonparametric approaches |
公开日期: | 2007 |
摘要: | Case-parent trio design常被用在遗传流行病学研究中,相较于其他的传统方法,例如:affected-sib-pair (ASP) sign,case-parent trio design更适合应用在罕见疾病。Liang 等人在2001年时根据case-parent trio design提出一种疾病基因相关定位的方法,他们利用偏好传递统计量(expected preferential-transmission statistic)估计疾病基因的位置。相较于传统的TDT方法,他们指出,这个方法不但较有效力,且可以应用于更广泛的资料。此外,除了利用假设检定去寻找疾病基因的位置,这个方法还能对疾病基因位点,提供准确的估计值及其相对应的标准差,以对这疾病位置作推论。因为许多复杂的疾病是由基因和环境因素的交互作用所造成,因此,加入这些基因或环境因素于三元体的资料分析,应能对疾病基因位点,做更精准的定位。在本研究中,我们用case-parent trios 的资料,分别利用有母数和无母数的方法,将相关的共变数并入模型中,以帮助我们估计疾病基因的位置。模拟结果和兔唇资料分析均显示,估计疾病基因位置时,加入共变数,会使得估计值更有效率。 Case-parant trio design is commonly used in genetic epidemiological family studies. It is more suitable for rare disorders than other conventional designs for family studies, such as affected-sib-pair (ASP) designs. Liang et al. (2001b) proposed a multipoint linkage disequilibrium (LD) mapping approach to localize disease genes based on a preferential-transmission statistic in the case-parent trio design. They found that their approach was more powerful and could accommodate a wider variety of data than the conventional TDT approach. In addition, instead of conducting hypothesis testing to search for a disease locus, it provided a precise estimate for a postulated disease locus along with its standard error, so that one can make inference for the disease locus. Most complex diseases involve both genetic and environmental components, incorporating genetic or environmental factors into the LD mapping may be helpful in localizing the disease locus. We therefore incorporated trait-related covariates into the LD mapping to estimate the disease locus through parametric and nonparametric models in the case-parent trio design in the present study. Simulation studies and the example of oral cleft study both suggested that incorporating covariates into the LD mapping approach helps a great deal to improve efficiency in localizing the disease locus. |
URI: | http://140.113.39.130/cdrfb3/record/nctu/#GT009526525 http://hdl.handle.net/11536/39006 |
显示于类别: | Thesis |
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