Causal relationships between potential risk factors and chronic rhinosinusitis: a bidirectional two-sample Mendelian randomization study

Abstract

Purpose Smoking, alcohol consumption, allergic rhinitis (AR), asthma, and obesity are associated with chronic rhinosinusitis (CRS), albeit the causal relationships between them remain elusive. Therefore, we conducted a bidirectional two-sample Mendelian randomization (MR) study to investigate the bidirectional causal effects between these potential risk factors and CRS. Methods The data for daily cigarette consumption, age of smoking initiation, weekly alcohol consumption, AR, asthma, body mass index (BMI), and CRS were drawn from large sample size genome-wide association studies. Single-nucleotide polymorphisms associated with each exposure were considered instrumental variables in this study. We investigated causal effects by using the inverse-variance weighted (IVW) method with random effects, and weighted median and MR–Egger methods were used for sensitivity analyses. Pleiotropic effects were detected and corrected by the MR pleiotropy residual sum and outlier test and MR–Egger model. Results We found the causal effects of daily cigarette consumption (IVW, OR = 1.15, 95% CI 1.00−1.32, p = 0.046), AR (IVW, OR = 4.77, 95% CI 1.61−14.13, p = 0.005), asthma (IVW, OR = 1.45, 95% CI 1.31 − 1.60, p < 0.001), and BMI (IVW, OR = 1.05, 95% CI 1.00−1.09, p = 0.028) on CRS. Furthermore, we found a causal effect of CRS on asthma (IVW OR = 1.08, 95% CI 1.05−1.12, p < 0.001). Conclusions We confirmed the causal effects of daily cigarette consumption, AR, asthma, and BMI on CRS, and the causal effect of CRS on asthma, while no causal relationship between age of smoking initiation, weekly alcohol consumption, and CRS was found. These findings are expected to provide high-quality causal evidence for clinical practice and the pathogenesis of CRS and asthma. Supplementary Information The online version contains supplementary material available at 10.1007/s00405-022-07798-6.

Causal Relationships of 38 Risk Factors with Chronic Rhinosinusitis: A Mendelian Randomization Study

“…Interestingly, in contrast to numerous observational studies and a prior MR inquiry 15,36,37 , our research discovered no evidence supporting an association between BMI and CRS. Observational studies often grapple with confounding factors and may encounter issues of reverse causality.…”

“…Several observational studies have consistently highlighted connections between AR, asthma, and CRS 7,34 . Moreover, a prior MR study has rmly established a causal link among these conditions 15 . Our ndings align with this conclusion, as we have replicated it using the latest CRS data from FinnGen R10.…”

“…Consequently, MR studies can effectively mitigate the in uence of confounding factors and avoid reverse causality 14 . However, to date, only a limited number of MR studies have examined the associations between a small set of risk factors and CRS 15 . In response to this gap, our study aims to comprehensively investigate the causal relationship between 38 genetically predicted risk factors and CRS using a two-sample MR approach.…”

Obesity and risk for respiratory diseases: a Mendelian randomization study

“…MR falls between interventional epidemiology and observational epidemiology in terms of the hierarchy of evidence ( 32 ). However, there have already been some MR studies on the associations between respiratory illnesses and obesity ( 20 – 22 , 33 ). There are at least two limitations in their studies.…”

“…Meta-analyses have found that an increase in BMI is associated with an increased risk of pulmonary embolism ( 17 ) and a reduced risk of COPD ( 18 ). There have previously been several Mendelian randomization (MR) analyses that focus on the association between body mass index and respiratory conditions including asthma ( 19 ), COPD ( 20 ), pneumonia ( 21 ), and chronic rhinosinusitis ( 22 ). On the one hand, their study was limited to employing BMI as the only indicator of obesity and did not evaluate the impact of body fat distributions.…”