Traditional observational studies often struggle to establish causal links between CIPs and allergic diseases due to biases and reverse causality.
16 Biases arise from confounding factors such as environmental exposures, lifestyle choices, and comorbidities that can influence both CIP levels and disease risk.
16,17 Reverse causality occurs when the disease itself alters CIP levels, making it challenging to discern cause from effect. In AC research, these challenges are intensified by diverse environmental and genetic factors.
7,18 Environmental influences include exposure to allergens such as pollen, dust mites, and pet dander, as well as air pollution and climate variations.
1,6 Genetic predispositions, particularly variations in genes regulating immune responses, further complicate the landscape.
5 The interplay of these factors introduces significant variability, hindering the isolation of specific causal relationships. Mendelian randomization (MR) offers a solution by using genetic variants as instrumental variables to infer causality.
19 Because genetic variants are randomly assigned at conception, they are generally free from the confounding factors and reverse causation that plague observational studies.
17,19 This method enhances the robustness of causal inferences, providing clearer insights into disease etiology.
17 For example, a study by Zhou et al.
20 utilized MR to establish a causal link between atopic dermatitis and AC, demonstrating the utility of this approach in identifying causal relationships. Understanding these causal pathways is crucial for developing effective prevention and treatment strategies for AC. By minimizing biases inherent in traditional studies, MR enables a more accurate assessment of the role of CIPs in allergic diseases, paving the way for innovative therapeutic interventions.
18 In this study, we pioneered the use of a mediated MR approach to explore the roles of 1400 MBs in the association of 91 CIPs with AC. By integrating genome-wide association study (GWAS) data and relevant biomarkers, we aimed to illuminate the intricate connections between genetic susceptibility, inflammatory responses, and allergic diseases. Our findings promise to deepen our understanding of this prevalent allergic condition, ultimately guiding the development of targeted and effective interventions.