A focusing framework for testing bi-directional causal effects in Mendelian randomization

• 成果类型: Article
• 署名作者: Li, Sai; Ye, Ting
• 署名单位: Renmin University of China; University of Washington; University of Washington Seattle
• 刊物名称: JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY
• ISSN/ISSBN: 1369-7412
• DOI: 10.1093/jrsssb/qkae101
• 发表日期: 2025
• 页码: 529-548
• 关键词: invalid instruments; pleiotropy; inference; models; HEALTH

摘要

Mendelian randomization (MR) is a powerful method that uses genetic variants as instrumental variables to infer the causal effect of a modifiable exposure on an outcome. We study inference for bi-directional causal relationships and causal directions with possibly pleiotropic genetic variants. We show that assumptions for common MR methods are often impossible or too stringent given the potential bi-directional relationships. We propose a new focusing framework for testing bi-directional causal effects and it can be coupled with many state-of-the-art MR methods. We provide theoretical guarantees for our proposal and demonstrate its performance using several simulated and real datasets.