Wei Qinyu, Chen Yuanli, Zeng Zheng, Shu Chang, Long Lu, Lu Jianhua, Huang Yangxin, Yin Ping
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, Florida, United States of America.
PLoS One. 2014 Dec 23;9(12):e114892. doi: 10.1371/journal.pone.0114892. eCollection 2014.
We propose a new method for family-based tests of association and linkage called transmission/disequilibrium tests incorporating unaffected offspring (TDTU). This new approach, constructed based on transmission/disequilibrium tests for quantitative traits (QTDT), provides a natural extension of the transmission/disequilibrium test (TDT) to utilize transmission information from heterozygous parents to their unaffected offspring as well as the affected offspring from ascertained nuclear families. TDTU can be used in various study designs and can accommodate all types of independent nuclear families with at least one affected offspring. When the study sample contains only case-parent trios, the TDTU is equivalent to TDT. Informative-transmission disequilibrium test (i-TDT) and generalized disequilibrium test(GDT) are another two methods that can use information of both unaffected offspring and affected offspring. In contract to i-TDT and GDT, the test statistic of TDTU is simpler and more explicit, and can be implemented more easily. Through computer simulations, we demonstrate that power of the TDTU is slightly higher compared to i-TDT and GDT. All the three methods are more powerful than method that uses affected offspring only, suggesting that unaffected siblings also provide information about linkage and association.
我们提出了一种新的基于家系的关联和连锁检验方法，称为纳入未患病后代的传递/不平衡检验（TDTU）。这种新方法基于定量性状的传递/不平衡检验（QTDT）构建，它是传递/不平衡检验（TDT）的自然扩展，用于利用杂合子父母向其未患病后代以及来自确定核心家系的患病后代的传递信息。TDTU可用于各种研究设计，并能适用于所有至少有一个患病后代的独立核心家系。当研究样本仅包含病例-父母三联体时，TDTU等同于TDT。信息性传递不平衡检验（i-TDT）和广义不平衡检验（GDT）是另外两种可以利用未患病后代和患病后代信息的方法。与i-TDT和GDT不同，TDTU的检验统计量更简单、更明确，并且更容易实现。通过计算机模拟，我们证明TDTU的效能比i-TDT和GDT略高。这三种方法都比仅使用患病后代的方法更有效，这表明未患病的同胞也能提供有关连锁和关联的信息。
