de Haan Hugoline G, Siegerink Bob, van Hylckama Vlieg Astrid
Leids Universitair Medisch Centrum, afd. Klinische Epidemiologie, Leiden.
Ned Tijdschr Geneeskd. 2014;158:A7547.
Classical observational studies into the causal relationship between a risk factor and a disease sometimes result in contradictory and spurious findings. This is due to confounding factors. It is not possible to conclude from the results of classical observational studies whether a specific risk factor may be a suitable target for future treatments. A solution is to conduct a Mendelian randomization analysis, which uses genetic variation as a surrogate marker for the risk factor. Mendelian randomisation is based on the idea that characteristics and environmental factors are proportionately divided into carriers and non-carriers of various genetic variants. Mendelian randomisation can be used only if there is a robust relationship between the genetic variant and the risk factor, if the genetic variant is not associated with other factors that confound the relationship between the risk factor and the disease, and if the genetic variant has an effect on the disease only via the risk factor, i.e. not via other biological mechanisms.
针对风险因素与疾病之间因果关系的经典观察性研究有时会得出相互矛盾且虚假的结果。这是由于混杂因素所致。从经典观察性研究的结果中无法得出特定风险因素是否可能成为未来治疗的合适靶点。一种解决办法是进行孟德尔随机化分析，该分析将基因变异用作风险因素的替代标志物。孟德尔随机化基于这样一种理念，即特征和环境因素会按比例分配到各种基因变异的携带者和非携带者中。只有当基因变异与风险因素之间存在稳健的关系、基因变异与其他混淆风险因素和疾病之间关系的因素无关，且基因变异仅通过风险因素而非其他生物学机制对疾病产生影响时，才能使用孟德尔随机化。
