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孟德尔随机化研究中的生存偏差:对因果推断的威胁。

Survival Bias in Mendelian Randomization Studies: A Threat to Causal Inference.

机构信息

From the Department of Cardiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.

Section of Gerontology and Geriatrics, Department of Internal Medicine, LUMC, Leiden, the Netherlands.

出版信息

Epidemiology. 2019 Nov;30(6):813-816. doi: 10.1097/EDE.0000000000001072.


DOI:10.1097/EDE.0000000000001072
PMID:31373921
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6784762/
Abstract

It has been argued that survival bias may distort results in Mendelian randomization studies in older populations. Through simulations of a simple causal structure we investigate the degree to which instrumental variable (IV)-estimators may become biased in the context of exposures that affect survival. We observed that selecting on survival decreased instrument strength and, for exposures with directionally concordant effects on survival (and outcome), introduced downward bias of the IV-estimator when the exposures reduced the probability of survival till study inclusion. Higher ages at study inclusion generally increased this bias, particularly when the true causal effect was not equal to null. Moreover, the bias in the estimated exposure-outcome relation depended on whether the estimation was conducted in the one- or two-sample setting. Finally, we briefly discuss which statistical approaches might help to alleviate this and other types of selection bias. See video abstract at, http://links.lww.com/EDE/B589.

摘要

有人认为,生存偏差可能会扭曲老年人群中孟德尔随机化研究的结果。通过对一个简单因果结构的模拟,我们研究了在影响生存的暴露因素的情况下,工具变量(IV)估计值可能会产生偏差的程度。我们观察到,在选择生存的情况下,工具的强度会降低,并且对于在生存(和结果)方面具有方向一致影响的暴露因素,当暴露因素降低了研究纳入时的生存概率时,IV 估计值会引入向下偏差。研究纳入时的年龄较高通常会增加这种偏差,特别是当真实的因果效应不等于零时。此外,估计的暴露-结果关系中的偏差取决于估计是在单样本还是双样本设置中进行的。最后,我们简要讨论了哪些统计方法可能有助于减轻这种和其他类型的选择偏差。请观看视频摘要,网址为:http://links.lww.com/EDE/B589。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b872/6784762/913bb2f3cd80/ede-30-813-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b872/6784762/58e05eee5798/ede-30-813-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b872/6784762/913bb2f3cd80/ede-30-813-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b872/6784762/58e05eee5798/ede-30-813-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b872/6784762/913bb2f3cd80/ede-30-813-g003.jpg

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本文引用的文献

[1]
Collider scope: when selection bias can substantially influence observed associations.

Int J Epidemiol. 2018-2-1

[2]
Survivor bias in Mendelian randomization analysis.

Biostatistics. 2018-10-1

[3]
Impact of Selection Bias on Estimation of Subsequent Event Risk.

Circ Cardiovasc Genet. 2017-10

[4]
Mortality selection in a genetic sample and implications for association studies.

Int J Epidemiol. 2017-8-1

[5]
Instrumental Variable Analyses and Selection Bias.

Epidemiology. 2017-5

[6]
Quantifying the extent to which index event biases influence large genetic association studies.

Hum Mol Genet. 2017-3-1

[7]
Diagnostics for Confounding of Time-varying and Other Joint Exposures.

Epidemiology. 2016-11

[8]
Using family members to augment genetic case-control studies of a life-threatening disease.

Stat Med. 2016-7-20

[9]
Genetic studies of body mass index yield new insights for obesity biology.

Nature. 2015-2-12

[10]
Mendelian randomization studies in the elderly.

Epidemiology. 2015-3

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