Family-based association test for time-to-onset data with time-dependent differences between the hazard functions

被引:14
作者
Jiang, HY
Harrington, D
Raby, BA
Bertram, L
Blacker, D
Weiss, ST
Lange, C
机构
[1] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA USA
[4] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA
[5] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA
关键词
weighted family-based association test; logrank test; censoring; quantitative trait;
D O I
10.1002/gepi.20132
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
In genetic association studies, the differences between the hazard functions for the individual genotypes are often time-dependent. We address the non-proportional hazards data by using the weighted logrank approach by Fleming and Harrington [1981]:Commun Stat-Theor M 10:763-794. We introduce a weighted FBAT-Logrank whose weights are based on a non-parametric estimator for the genetic marker distribution function under the alternative hypothesis. We show that the computation of the marker distribution under the alternative does not bias the significance level of any subsequently computed FBAT-statistic. Hence, we use the estimated marker distribution to select the Fleming-Harrington weights so that the power of the weighted FBAT-Logrank test is maximized. In simulation studies and applications to an asthma study, we illustrate the practical relevance of the new methodology. In addition to power increases of 100% over the original FBAT-Logrank test, we also gain insight into the age at which a genotype exerts the greatest influence on disease risk.
引用
收藏
页码:124 / 132
页数:9
相关论文
共 21 条
[21]   Family-based association studies [J].
Zhao, HY .
STATISTICAL METHODS IN MEDICAL RESEARCH, 2000, 9 (06) :563-587