Detecting a Weak Association by Testing its Multiple Perturbations: a Data Mining Approach

Many risk factors/interventions in epidemiologic/biomedical studies are of minuscule effects. To detect such weak associations, one needs a study with a very large sample size (the number of subjects, n). The n of a study can be increased but unfortunately only to an extent. Here, we propose a novel method which hinges on increasing sample size in a different direction–the total number of variables (p). We construct a p-based ‘multiple perturbation test', and conduct power calculations and computer simulations to show that it can achieve a very high power to detect weak associations when p can be made very large. As a demonstration, we apply the method to analyze a genome-wide association study on age-related macular degeneration and identify two novel genetic variants that are significantly associated with the disease. The p-based method may set a stage for a new paradigm of statistical tests.