Family-based tests of association between a genetic marker and a disease constitute a common design to dissect the genetic architecture of complex traits. The FBAT software is one of the most popular tools to perform ...Family-based tests of association between a genetic marker and a disease constitute a common design to dissect the genetic architecture of complex traits. The FBAT software is one of the most popular tools to perform such studies. However, researchers are also often interested in the genetic contribution to a more specific manifestation of the phenotype (e.g. severe vs. non-severe form) known as a secondary outcome. Here, what we demonstrate is the limited power of the classical formulation of the FBAT statistic to detect the effect of genetic variants that influence a secondary outcome, in particular when these variants also impact on the onset of the disease, the primary outcome. We prove that this loss of power is driven by an implicit hypothesis, and we propose a derivation of the original FBAT statistic, free from this implicit hypothesis. Finally, we demonstrate analytically that our new statistic is robust and more powerful than FBAT for the detection of association between a genetic variant and a secondary outcome.展开更多
Count data with excess zeros encountered in many applications often exhibit extra variation. Therefore, zero-inflated Poisson(ZIP) model may fail to fit such data. In this paper, a zero-inflated double Poisson model(Z...Count data with excess zeros encountered in many applications often exhibit extra variation. Therefore, zero-inflated Poisson(ZIP) model may fail to fit such data. In this paper, a zero-inflated double Poisson model(ZIDP), which is generalization of the ZIP model, is studied and the score tests for the significance of dispersion and zero-inflation in ZIDP model are developed. Meanwhile, this work also develops homogeneous tests for dispersion and/or zero-inflation parameter, and corresponding score test statistics are obtained. One numerical example is given to illustrate our methodology and the properties of score test statistics are investigated through Monte Carlo simulations.展开更多
基金supported by the Programme Blanc de l’Agence National de la Recherche.
文摘Family-based tests of association between a genetic marker and a disease constitute a common design to dissect the genetic architecture of complex traits. The FBAT software is one of the most popular tools to perform such studies. However, researchers are also often interested in the genetic contribution to a more specific manifestation of the phenotype (e.g. severe vs. non-severe form) known as a secondary outcome. Here, what we demonstrate is the limited power of the classical formulation of the FBAT statistic to detect the effect of genetic variants that influence a secondary outcome, in particular when these variants also impact on the onset of the disease, the primary outcome. We prove that this loss of power is driven by an implicit hypothesis, and we propose a derivation of the original FBAT statistic, free from this implicit hypothesis. Finally, we demonstrate analytically that our new statistic is robust and more powerful than FBAT for the detection of association between a genetic variant and a secondary outcome.
基金Supported in part by the National Natural Science Foundation of China under Grant No.11271193 and 11571073the Natural Science Foundation of Jiangsu Province under Grant No.BK20141326
文摘Count data with excess zeros encountered in many applications often exhibit extra variation. Therefore, zero-inflated Poisson(ZIP) model may fail to fit such data. In this paper, a zero-inflated double Poisson model(ZIDP), which is generalization of the ZIP model, is studied and the score tests for the significance of dispersion and zero-inflation in ZIDP model are developed. Meanwhile, this work also develops homogeneous tests for dispersion and/or zero-inflation parameter, and corresponding score test statistics are obtained. One numerical example is given to illustrate our methodology and the properties of score test statistics are investigated through Monte Carlo simulations.
