Abstract

We respond to criticisms of Mendelian randomization (MR) by Mukamal, Stampfer and Rimm (MSR). MSR consider that MR is receiving too much attention and should be renamed. We explain how MR links to Mendel’s laws, the origin of the name and our lack of concern regarding nomenclature. We address MSR’s substantive points regarding MR of alcohol and cardiovascular disease, an issue on which they dispute the MR findings. We demonstrate that their strictures with respect to population stratification, confounding, weak instrument bias, pleiotropy and confounding have been addressed, and summarise how the field has advanced in relation to the issues they raise. We agree with MSR that “the hard problem of conducting high-quality, reproducible epidemiology” should be addressed by epidemiologists. However we see more evidence of confrontation of this issue within MR, as opposed to conventional observational epidemiology, within which the same methods that have demonstrably failed in the past are simply rolled out into new areas, leaving their previous failures unexamined.

中文翻译：

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孟德尔定律、孟德尔随机化和观测数据中的因果推理：实质性和命名问题。

摘要

我们回应 Mukamal、Stampfer 和 Rimm (MSR) 对孟德尔随机化 (MR) 的批评。MSR认为MR受到了太多关注，应该更名。我们解释了 MR 如何与孟德尔定律联系起来、名称的起源以及我们对命名法的不关心。我们讨论了 MSR 关于酒精和心血管疾病 MR 的实质性观点，他们在这个问题上对 MR 发现提出了异议。我们证明他们在人口分层、混杂、弱仪器偏差、多效性和混杂方面的限制已经得到解决，并总结了该领域在他们提出的问题方面的进展情况。我们同意 MSR 的观点，即“进行高质量、可重复的流行病学研究的难题”应该由流行病学家解决。然而，我们在 MR 中看到了更多关于这一问题的证据，这与传统的观察流行病学不同，在传统的观察流行病学中，过去明显失败的相同方法只是简单地推广到新领域，而没有对以前的失败进行检验。