Growing scientific evidence suggests that intricate interactions of genetic risk factors with environmental exposures play a major role in the development of chronic pain conditions. In studies of relative contribution of an individual’s genetic composition to the perception of pain, the general characteristics of pain sensitivity are typically measured by a wide range of different, yet possibly etiologically related pain phenotypes. Testing each of these pain-perception traits individually is subject to problems of multiple testing and low statistical power. Furthermore, pain-related traits may share common etiology and comprise binary, categorical, and quantitative measurements. In the current study, we propose a novel statistical approach for simultaneous testing of multiple correlated phenotypes, including quantitative binary, categorical or a combination thereof, with the flexibility of adjusting for other covariates. We illustrate our approach with the association analysis between groups of multiple pleiotropic phenotypes and genetic variants of the P2RX7 gene from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study.
Zaykin, Dmitri V.; Qing, L.; Slade, G. D.; Dubner, R.; Fillingim, R. B.; Greenspan, J. D.; Ohrbach, R.; Maixner, W.; Diatchenko, L. B.; and Vsevolozhskaya, Olga A., "Functional Linear Models Extensions Uncover Pleiotropic Effects of Chronic Pain Phenotypes" (2015). Biostatistics Presentations. 1.