报告人：康国莲 教授

报告时间：10月11日9:00-10:00

报告地点：统计与数据科学学院 109会议室

报告题目：A Novel One-Sample Mendelian Randomization Approach for Count-type Outcome Robust to Correlated and Uncorrelated Pleiotropic Effects

报告摘要：In individuals with single gene mutated recessive sickle cell disease (SCD), mutations in SCD modifier genes, such as BCL11A, can lead to increased levels of total fetal hemoglobin (HbF), which is associated with a reduced number of hospitalizations. Establishing a causal relationship between HbF levels and hospitalization rates is challenging and ideally requires a randomized clinical trial. However, Mendelian randomization (MR) provides a valid approach for exploring this relationship using observational data. Yet, MR traditionally lacks methods suited for count-type outcome data. To address this, we propose two novel one-sample Mendelian randomization (MR) approaches for causal inference with count-type health outcomes, designed to handle both equidispersion and overdispersion scenarios. Selecting valid single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) poses a key challenge for MR approaches, as it requires meeting the necessary IV assumptions. To bolster the proposed approaches by addressing violations of IV assumptions, we incorporate a process for removing invalid SNPs that violate the assumptions. In simulations, our proposed approaches demonstrate robustness to the violations, delivering valid estimates and interpretable type I errors and statistical powers. This increases the practical applicability of the models. We applied the proposed approaches to evaluate the causal effect of HbF on the vaso-occlusive crisis and acute chest syndrome (ACS) events in patients with SCD and revealed the causal relation between HbF and ACS events in these patients. We also developed a user-friendly Shiny web application to facilitate researchers' exploration of causal relations.

报告人简介：康国莲，博士，现为美国圣裘德儿童研究医院生物统计系教授。2006年博士毕业于中国科学院数学与系统科学研究院系统所。随后在密歇根州立大学、阿拉巴马大学伯明翰、宾夕法尼亚大学做访问学者和博士后研究。一直从事统计遗传、临床实验、遗传流行病、生物统计学等研究。已发表SCI学术论文153篇，其中包括Nature Genetics, The New England Journal of Medicine, Nature Cell Biology, Blood, Journal of Clinical Oncology等，被独立引用多于3800次。其多个研究成果被世界著名媒体报道（美国： NewsRX.com 和ScienceDaily， 委内瑞拉: International Adaptogens，英国Nature Review Genetics））并被收录于书《Transgénicos》 （古巴）。现合作主持和参与由美国NIH/NHLBI资助的14项高水平科研项目。设计了多于50多个临床试验protocol. 担任NIH(USA)和DPFS(UK)基金评审专家,是多个国际期刊的副主编和编委。