disease, and another method (multi-trait-based conditional and joint analysis, or mtCOJO) to estimate the effect of a risk factor on disease conditioning on other risk factors. All methods developed in this study only require summary-level data (with LD between genetic variants from a reference sample with individual-level data), providing a great flexibility to integrate data from multiple studies. We apply the methods to publicly available data of very large sample sizes (n = up to 405,072 for risk factors and 184,305 for diseases) to test the causal associations between health risk factors such as BMI, serum cholesterol levels and blood pressure levels and a range of human common diseases. Our study develops powerful tools to integrate summary data from large studies to infer causality, and provides important candidates to be prioritized for further studies in medical research and for drug discovery.