PheWAS and clinical trials is important before pushing PheWAS further for making clinical decisions. Forty-seven percent of the previously-reported associations were successfully reproduced in this study, demonstrating this PheWAS' capability for working with clinical data. Additionally, several pleiotropic effects were discovered using this clinical data. Specifically, a block of SNPs on chromosome 7 were associated to both LDL-C phenotypes and the total cholesterol level according to this study. For clinical relevance, more research need to be done to validate the pleiotropic effect obtained from PheWAS. Limitations Despite the promising potentials, PheWAS has some potential limitations: Statistical limitation: Bonferroni correction is potentially not addressing the entirety of the dataset (it may be prohibitively conservative). ICD9-notation limitation: not every phenotype can be represented in an ICD9 code. One ICD9 code can have a high variability, making it impossible to assess the validity of phenotypes that are coded to ICD9 for all the patients. Association limitation: upon performing a regression analysis for variant-phenotype association, covariates like age and sex may contribute in the resulting phenotypes. A simple regression analysis would fail to take into account these covariates. Therefore, a follow-up phenotype-specific validation need to be done, which ideally would include information about the patient's covariates. Every novel pleiotropy discovery will need further biological validation to ensure that the data-driven association is not a mere statistical coincident. References External links Website listing catalogs of PheWASs Genetic epidemiology Genomics