Contextualizing selection bias in Mendelian randomization: how bad is it likely to be?
Contextualizing selection bias in Mendelian randomization: how bad is it likely to be?
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DOI：
10.1093/ije/dyy202
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发表时间：
2019-06-01
影响因子：
7.7
通讯作者：
Burgess S
中科院分区：
文献类型：
--
作者：
Gkatzionis A;Burgess S
选择偏倚影响孟德尔随机化研究，当选择研究样本取决于遗传变异和风险因素-结果关联的混杂因素之间的碰撞者时。然而，与其他潜在的偏倚相比，孟德尔随机化的选择偏倚的相对重要性尚不清楚。我们进行了广泛的模拟研究，以评估选择偏倚对典型孟德尔随机化研究的影响。我们认为逆概率加权作为一种潜在的方法，减少选择偏差。最后，我们研究了选择偏倚是否可以解释最近报道的发现，即脂蛋白（a）不是既往冠心病患者心血管死亡的因果危险因素。在我们的模拟研究中，选择偏差对偏差和1型错误率有严重影响，但只有当选择效应较大时。对于风险因素对选择的中度影响，偏倚通常较小，并且1型错误率膨胀并不显著。当选择模型被正确指定时，逆概率加权改善了偏倚，但当选择偏倚为中度且模型被错误指定时，逆概率加权增加了偏倚。在脂蛋白（a）的例子中，强遗传关联和强混杂效应的选择意味着报告的心血管死亡率的无效效应可以合理地解释为选择偏倚。选择偏倚会对孟德尔随机化研究产生不利影响，但其影响可能小于其他偏倚。当风险因素和混杂因素对选择的影响特别大时，选择偏倚是实质性的。
Selection bias affects Mendelian randomization investigations when selection into the study sample depends on a collider between the genetic variant and confounders of the risk factor–outcome association. However, the relative importance of selection bias for Mendelian randomization compared with other potential biases is unclear. We performed an extensive simulation study to assess the impact of selection bias on a typical Mendelian randomization investigation. We considered inverse probability weighting as a potential method for reducing selection bias. Finally, we investigated whether selection bias may explain a recently reported finding that lipoprotein(a) is not a causal risk factor for cardiovascular mortality in individuals with previous coronary heart disease. Selection bias had a severe impact on bias and Type 1 error rates in our simulation study, but only when selection effects were large. For moderate effects of the risk factor on selection, bias was generally small and Type 1 error rate inflation was not considerable. Inverse probability weighting ameliorated bias when the selection model was correctly specified, but increased bias when selection bias was moderate and the model was misspecified. In the example of lipoprotein(a), strong genetic associations and strong confounder effects on selection mean the reported null effect on cardiovascular mortality could plausibly be explained by selection bias. Selection bias can adversely affect Mendelian randomization investigations, but its impact is likely to be less than other biases. Selection bias is substantial when the effects of the risk factor and confounders on selection are particularly large.
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