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A joint model for nonparametric functional mapping of longitudinal trajectory and time-to-event

DOI: 10.1186/1471-2105-7-138

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Abstract:

We present a joint statistical model for functional mapping of dynamic traits in which the event times and longitudinal traits are taken to depend on a common set of genetic mechanisms. By fitting the Legendre polynomial of orthogonal properties for the time-dependent mean vector, our model does not rely on any curve, which is different from earlier parametric models of functional mapping. This newly developed nonparametric model is demonstrated and validated by an example for a forest tree in which stemwood growth and the time to first flower are jointly modelled.Our model allows for the detection of specific QTL that govern both longitudinal traits and developmental processes through either pleiotropic effects or close linkage, or both. This model will have great implications for integrating longitudinal and event data to gain better insights into comprehensive biology and biomedicine.Although there has been a upsurge of interest in jointly modelling longitudinal and event data during the last decade [1-9], no statistical models have been developed to characterize the shared genetic basis for these two types of traits. In biomedicine, the identification of specific genetic variants responsible for an HIV patient's time-dependent CD4 count and for the time to onset of AIDS symptoms can help to design individualized drugs to control this patient's progression to AIDS. Similarly, in studies of prostate cancer, a shared genetic basis between prostate specific antigen, repeatedly measured for patients following treatment for prostate cancer, and the time to disease recurrence can be used to make optimal treatment schedules for patients. In plants, knowledge about whether the genetic loci for reproductive behaviors, such as the time to first flower and the time to form seeds, also govern growth rates and sizes of plants helps to understand the etiology of plant's adaptation to the environment in which they are grown.The genetic mapping of quantitative trait loci (QTL) t

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