Mendelian Randomization is a Powerful Tool for Improving Psoriasis Understanding

A systematic review on Mendelian Randomization (MR) studies in the setting of psoriasis (PsO) and psoriatic arthritis (PsA) was published in Journal of Investigative Dermatology.

This review included 27 studies found in a literature search performed through October 2022 by researchers from University of California, San Francisco.

Patients with PsO often have comorbidities, including cardiometabolic and psychiatric conditions. There has been evidence that certain modifiable behaviors, such as alcohol consumption, smoking, and obesity can affect the incidence and severity of PsO. However, directionality and the magnitude of such relationships remains unclear.

The MR research method allows for researchers to evaluate causation without the need for randomized controlled trials and in the absence of ascertainment bias or confounding factors.

Nevertheless, this approach is not infallible, and MR is reliant on 3 important assumptions: that the associations between single nucleotide polymorphisms (SNPs) and variables of interest are robust, the relationships between SNPs and outcomes have not been confounded by horizontal pleiotropy, and SNPs themselves are not associated with confounding factors.

There have been 4 MR studies published examining the role of alcohol consumption in the development of PsO. Three of these studies reported that genetic predisposition to consuming more alcohol weekly did not relate with PsO; however, the fourth study in a population of individuals from Spain found an inverse relationship between alcohol consumption and PsO development (odds ratio [OR], 0.87).

Regarding the relationship between smoking and PsO, 2 studies evaluated different aspects of smoking, such as initiation, quantity, cessation, and lifetime use, and a consistent positive relationship between smoking and PsO incidence was reported.

For obesity, all 5 studies evaluating body mass index and PsO reported a significant relationship (OR range, 1.09-1.59). In addition, results of another study found that unfavorable adiposity increased risk for developing PsO (OR, 2.11) and another found that body size in childhood predicted PsO (OR, 2.23) and PsA (OR, 1.64) onset.

Several MR analyses have related the development of PsO with comorbidities, such as type 2 diabetes (adjusted OR [aOR], 1.35), coronary atherosclerosis (aOR, 1.14), inflammatory bowel disease (OR, 1.13), Crohn disease (OR, 1.13), and major depressive disorder (OR, 1.41).

Although no clinical biomarkers have been established as markers for PsO or PsA risk, findings from MR studies suggest several markers, such as interleukin (IL)-12B for PsO (OR, 0.84) and PsA (OR, 0.79) risk.

Review authors conclude, “MR has immense potential to uncover the impact of health behaviors and other medical risk factors for the development of PsO and PsA. It is important to keep in mind the limitations and best practices for conducting and interpreting such studies. However, it is exciting to see the potential of MR in enabling precision medicine to better allow the recommendation of individualized behavioral, diagnostic, and therapeutic changes.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.