Investigating causal relationships between Body Mass Index and risk of atopic dermatitis: a Mendelian randomization analysis

Abstract

Population studies suggest that atopic dermatitis (AD) is associated with an increased risk of obesity, however a causal relationship between these two conditions remains to be established. We therefore use Mendelian randomization (MR) to evaluate whether obesity and AD are causally interlinked. We used summary statistics extracted from genome wide association studies of Body Mass Index (BMI) and AD. MR analysis was performed in both directions to establish the direction of causality between BMI and AD. We find that genetically determined increase in adiposity is associated with increased risk of AD (odds ratio of AD 1.08 [95% CI 1.01 to 1.14; p = 0.015] per unit increase in BMI). Conversely, genetically determined increased risk of AD is not associated with a higher BMI (change in BMI attributable to AD based on genetic information: 0.00; 95% CI − 0.02 to 0.02; p = 0.862). There was no evidence for confounding of these genetic analyses by horizontal pleiotropy. Our results indicate that the association of AD with obesity is likely to reflect a causal role for adiposity in the development of AD. Our findings enhance understanding of the etiology of AD, and the basis for experimental studies to evaluate the mechanistic pathways by which adiposity promotes AD.

Relationship between body mass index and atopic dermatitis: a Mendelian randomization approach in exploring causality: a critical appraisal

“…As a testament to the validity of this study’s findings, a recent publication by Yew et al . using MR analyses yielded similar conclusions 8 …”

“…As a testament to the validity of this study's findings, a recent publication by Yew et al using MR analyses yielded similar conclusions. 8 Given that AD often arises in childhood, the authors examined the causality of BMI on AD onset using SNPs associated with childhood obesity and reported a similar causal effect. While the implications on BMI causality on AD risk are intriguing, examining the clinical impact of an intervention on BMI as a means of reducing AD risk would need to be assessed with a clinical trial as this study's findings do not necessarily inform the clinical impact of a weight loss intervention in childhood on the onset of AD in later life.…”

Emerging Roles of Adipose Tissue in the Pathogenesis of Psoriasis and Atopic Dermatitis in Obesity

“…To investigate the causal relationship between AD and obesity, Yew, Y. W et al conducted a Mendelian randomization (MR) analysis using data extracted from genome-wide association studies (GWAS) of Body Mass Index (BMI) and AD (Yew et al, 2020). They found that increase in obesity determined by susceptible genes is associated with increased risk of AD (odds ratio of AD 1.08 [95% CI 1.01 to 1.14; p = 0.015] per unit increase in BMI).…”

Relationship of atopic dermatitis with obesity and its related inflammatory metabolic disturbances in an adult general population cohort

“…This is significant as it sets the scope and direction on current and future work to evaluate the observed links between obesity and AD. This finding has recently been published in a peer-reviewed journal [227].…”

“…Beyond a mere chronic skin condition, AD has been reported to be associated with adiposity as well as other co-morbidities in various epidemiological studies. This is further supplemented by recent evidence that genetically determined increase in adiposity is related to an increased risk of AD [227].…”