Lewy body disorders are characterized by extrapyramidal motor symptoms and a wide range of nonmotor features, including cognitive impairment, depression, psychosis, rapid eye movement sleep behavior disorder, and autonomic dysfunction. However, the constellation of problems and rate of symptom progression that each patient experiences vary substantially. There is widespread belief that genetic variation explains some of this phenotypic heterogeneity. Identifying specific genes that play such a role could uncover novel targets for drug development, improve our ability to predict prognosis on an individual level, and be of benefit in designing and analyzing data from clinical trials. To expand on the last point, randomized clinical trials provide information on the average treatment effect in a study population, but drug response and the occurrence of adverse effects often differ substantially among patients. Stratifying clinical trial participants by genotype might create subgroups that are more homogeneous in clinical profile and trajectory of decline, thus improving power to detect treatment effects.
Zabetian CP. The Clinical Profile of GBA-Related Lewy Body Disorders. JAMA Neurol. 2016;73(12):1403-1404. doi:10.1001/jamaneurol.2016.2546