Mendelian randomisation and the goal of inferring causation from observational studies in the vision sciences

Abstract

Purpose Randomised controlled trials (RCTs) allow reliable causal inferences to be drawn regarding the effectiveness of specific interventions. However, they are expensive to carry out, and not all exposure‐outcome relationships can be tested in an RCT framework: for example, it would be unethical to deliberately expose participants to a putative risk factor, or the time‐scale involved may be prohibitive. Mendelian randomisation (MR) has been proposed as an alternative approach for drawing causal inferences, with the major advantage that the method can often be applied to existing, cross‐sectional study datasets. Therefore, results from an MR study can be obtained much more quickly and cheaply than through an RCT. Recent findings The validity of causal inferences from an MR study are dependent on two key assumptions, neither of which can be tested fully. Nevertheless, several approaches have been proposed in the last 3 years that either highlight questionable results, or provide valid causal inference if the necessary assumptions are met only in part. Compared to certain other areas of clinical practice, the ophthalmic research community has been slow to adopt MR. Summary An MR study cannot match an RCT in its strength of evidence for a claim of causality. However, MR still has much to offer. In some circumstances, an MR study can provide causal insight into research questions that cannot be addressed by an RCT, while more generally, an MR study can be used to evaluate the supporting evidence before deciding to embark on a lengthy and costly RCT.

Genetically Determined Serum 25-Hydroxyvitamin D Is Associated with Total, Trunk, and Arm Fat-Free Mass: A Mendelian Randomization Study

“…A major advantage of MR analysis is that they are considerably less prone to confounding, residual bias, and reverse causation than conventional riskfactor epidemiology (22). MR analysis may also circumvent the financial, logistical and ethical limitations of randomised controlled trials (RCTs) and additionally, the data from such studies can inform the design of pilot RCTs and clinical trials by providing information for the potential magnitude of effect of nutrients on a given outcome in specific populations (23).…”

Association between overweight or obesity and the risk for childhood asthma and wheeze: An updated meta‐analysis on 18 articles and 73 252 children

“…A majority of longitudinal studies have shown that being overweight and suffering from obesity precede the onset of children asthma, yet findings from other studies indicate that children with asthma or presence of asthma history may be at higher risk of obesity . Actually, for many types of exposure in epidemiology, it is both impractical and unethical to randomize study participants to different “treatment” arms . At times, epidemiological data can be summarized to derive a relatively reliable estimate.…”

Association between birth weight and refractive error in adulthood: a Mendelian randomisation study

“…Previous investigations of the relationship between BW and refractive error have been restricted to observational study designs. Observational studies are susceptible to confounding, and therefore offer very limited potential for drawing causal inferences [17]. The aim of the current study was to test for a causal relationship between BW within the normal range and refractive error in adulthood.…”