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Abstract Horizontal pleiotropy poses challenges in Mendelian randomization (MR) by biasing causal estimates, particularly when using numerous instrumental variables (IVs). We propose MRZ, a method that leverages IV-outcome association z-scores modeled as a mixture distribution to distinguish causal effects from IV-specific pleiotropy.
The authors have declared no competing interest. This study was partially supported by the funding from National Natural Science Foundation of China (32170670 to YFP, 81902181 to JJN), the Project of MOE Key Laboratory of Geriatric Diseases and Immunology (JYN202401 to HGR), and Suzhou Basic Research Program (Medical Application Basic Research) (SKY2023147 to JJN).
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