Zhang Feng, Deng Hong-Wen
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, PR China.
Hum Hered. 2010;69(1):28-33. doi: 10.1159/000243151. Epub 2009 Oct 2.
Cryptic relatedness was suggested to be an important source of confounding in population-based association studies (PBAS). The magnitude and manner of cryptic relatedness affecting the performance of PBAS of continuous traits remain to be investigated. We simulated a set of related samples through biased sampling and inbreeding, and evaluated the power and type I error rates of simple association tests (SAT) without correcting for cryptic relatedness. We also used extended likelihood ratio tests (ELRT) to conduct PBAS accounting for cryptic relatedness, and compared it with genomic control (GC). Cryptic relatedness decreased the power as well as increased the type I error rates of SAT in both biased sampling and inbreeding models. The impact of cryptic relatedness on the performance of SAT appeared to be limited in the biased sampling model. However, cryptic relatedness in inbred populations may result in excessive false positive results of SAT. Compared with SAT and GC, ELRT obtained improved power and type I error rates under various scenarios. Ignoring cryptic relatedness may increase spurious association results in PBAS. Our ELRT provides a novel approach to control cryptic relatedness in PBAS of human continuous traits.
隐秘亲缘关系被认为是基于人群的关联研究（PBAS）中混杂因素的一个重要来源。影响连续性性状PBAS表现的隐秘亲缘关系的程度和方式仍有待研究。我们通过偏向抽样和近亲繁殖模拟了一组相关样本，并评估了未校正隐秘亲缘关系的简单关联检验（SAT）的功效和I型错误率。我们还使用扩展似然比检验（ELRT）来进行考虑隐秘亲缘关系的PBAS，并将其与基因组控制（GC）进行比较。在偏向抽样和近亲繁殖模型中，隐秘亲缘关系均降低了SAT的功效并增加了I型错误率。在偏向抽样模型中，隐秘亲缘关系对SAT表现的影响似乎有限。然而，近交群体中的隐秘亲缘关系可能导致SAT出现过多的假阳性结果。与SAT和GC相比，ELRT在各种情况下都获得了更好的功效和I型错误率。忽略隐秘亲缘关系可能会增加PBAS中虚假关联结果。我们的ELRT为控制人类连续性性状PBAS中的隐秘亲缘关系提供了一种新方法。
