Atopic dermatitis (AD), also known as eczema, is a common skin disorder that is highly heritable and affects over 20% of children worldwide. AD can cause dry skin, intense itching, rash, swollen skin, and oozing, leading to sleep deprivation and social embarrassment. It can also impair the quality of life not only of patients but also of their families. Earlier childhood AD is a strong predictor for adolescence or adulthood AD. Families with AD children of patients tend to utilize healthcare services more frequently and experience greater social and economic challenges than non-ADs.
Although AD is highly heritable, some modifiable environmental exposures, such as pollution, dry skin, stress, and obesity, are also found to be related to its development since these exposures can change gene expressions, called DNA methylation (DNAm), and can result in skin disorders. Investigating what environmental exposures cause DNAm and how DNAm causes AD will enable us to understand the underlying molecular mechanisms of this disease and allow public health efforts to predict and manage environmental exposures of AD more effectively at earlier stages of life, potentially reducing the burden of AD on patients, families, and healthcare systems. To this end, this proposed study aims to identify the causal effect of DNAm level due to modifiable environmental risk factors on AD using a two-step Mendelian Randomization (MR) test. We will use the Avon Longitudinal Study of Parents and Children dataset (ALSPAC, United Kingdom) for the analyses. The MR test is an epidemiological method designed to estimate the causal relationship of exposure with a disease in observational (non-experimental) data. In the two-step MR test, we first identify the causal effect of environmental factors on the DNAm. This DNAm will then be used in the second step to investigate the causal effect on AD. We expect to find the causal relationship between DNAm and AD. To our knowledge, this is the first study using the two-step MR test to investigate the causal relationship between DNAm level due to modifiable environmental exposures and AD.