Family-based association tests for sequence data, and comparisons with population-based association tests
Family-based association tests for sequence data, and comparisons with population-based association tests
复制标题
DOI：
10.1038/ejhg.2012.308
复制
发表时间：
2013-10-01
影响因子：
5.2
通讯作者：
Lin, Xihong
中科院分区：
文献类型：
--
作者：
Ionita-Laza, Iuliana;Lee, Seunggeun;Lin, Xihong
高通量测序技术的最新进展使得对许多复杂性状的大队列测序越来越有效。我们在这里讨论一类基于序列的关联测试，用于基于家族的设计，这些测试自然地对应于先前提出的基于群体的测试，包括经典的负担和方差成分测试。该框架允许直接比较基于序列的关联测试与基于家族和基于人群的设计之间的能力。我们表明，对于二分类特征，使用基于家族的控制结果与基于群体的设计相似（尽管基于家族的设计增加了测序成本），而对于连续特征（在随机样本中，没有确定），基于群体的设计可以显着更强大。基于人群的设计可能存在的一个缺点是，在存在人群分层的情况下，它们可能导致假阳性率增加，而基于家庭的设计对人群分层具有稳健性。我们还展示了一个应用于自闭症谱系障碍的小型外显子组测序家庭研究。测试是在公开可用的软件中实现的。
Recent advances in high-throughput sequencing technologies make it increasingly more efficient to sequence large cohorts for many complex traits. We discuss here a class of sequence-based association tests for family-based designs that corresponds naturally to previously proposed population-based tests, including the classical Burden and variance-component tests. This framework allows for a direct comparison between the powers of sequence-based association tests with family- vs population-based designs. We show that for dichotomous traits using family-based controls results in similar power levels as the population-based design (although at an increased sequencing cost for the family-based design), while for continuous traits (in random samples, no ascertainment) the population-based design can be substantially more powerful. A possible disadvantage of population-based designs is that they can lead to increased false-positive rates in the presence of population stratification, while the family-based designs are robust to population stratification. We show also an application to a small exome-sequencing family-based study on autism spectrum disorders. The tests are implemented in publicly available software.