CLIP test: a new fast, simple and powerful method to distinguish between linked or pleiotropic quantitative trait loci in linkage disequilibria analysis

An important question arises when mapping quantitative trait loci (QTLs) for genetically correlated traits: is the correlation due to pleiotropy (a single QTL affecting more than one trait) and/or close linkage (different QTLs that are physically close to each other and influence the traits)? In this article, we propose the Close Linkage versus Pleiotropism (CLIP) test, a fast, simple and powerful method to distinguish between these two situations. The CLIP test is based on the comparison of the square of the observed correlation between a combination of apparent effects at the marker level to the minimal value it can take under the pleiotropic assumption. A simulation study was performed to estimate the power and alpha risk of the CLIP test and compare it to a test that evaluated whether the confidence intervals of the two QTLs overlapped or not (CI test). On average, the CLIP test showed a higher power (68%) to detect close-linked QTLs than the CI test (43%) and a same alpha risk (4%)...

当针对遗传相关性状开展数量性状位点（quantitative trait loci, QTLs）定位研究时，一个关键问题随之浮现：该性状间的相关性究竟源自多效性（pleiotropy，即单个QTL同时影响多个性状）、紧密连锁（close linkage，即物理位置邻近且分别调控不同性状的不同QTL），还是二者共同作用？本文中，我们提出了紧密连锁与多效性检验（Close Linkage versus Pleiotropism, CLIP），这是一种快速、简洁且高效的方法，可用于区分上述两种情形。CLIP检验的核心原理为：将标记水平下表观效应组合间的观测相关性平方值，与多效性假设下该平方值所能达到的最小值进行对比。本研究通过模拟实验，估算了CLIP检验的统计效力与一类错误风险，并将其与一种通过判断两个QTL的置信区间是否重叠来开展检验的方法（CI检验）进行了对比。平均而言，CLIP检验检测紧密连锁QTL的统计效力（68%）高于CI检验（43%），且二者的一类错误风险一致，均为4%……