- 1Department of Dermatology and Allergy, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.
- 2Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
- 3Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.
- 4Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.
- 5Gastro Unit, Copenhagen University Hospital-Hvidovre, Copenhagen, Denmark.
Background: Psoriasis is observationally associated with a higher risk of non-alcoholic fatty liver disease (NAFLD); however, the causal relationship between the two diseases remains unclear.
Objective: We hypothesized that individuals with NAFLD or elevated liver fat content have higher risk of psoriasis and that NAFLD is a causal risk factor for psoriasis. We tested this using a Mendelian randomization approach.
Methods: We included 108,835 individuals from the Danish general population, including 1,277 individuals with psoriasis and 802 individuals with NAFLD according to ICD codes. To estimate liver fat content, a subset of the participants (N = 7,416) also had a CT scan performed. First, we tested whether a diagnosis of NAFLD or elevated liver fat content was observationally associated with risk of psoriasis. Subsequently, we used the genetic variants <i>PNPLA3</i> and <i>TM6SF2</i>, both strongly associated with NAFLD and high liver fat content, to test whether NAFLD was causally associated with increased risk of psoriasis.
Results: Observationally, individuals with vs. without a diagnosis of NAFLD had higher risk of psoriasis with an odds ratio of 2.03 (95% confidence interval 1.28-3.21). The risk of psoriasis increased in a stepwise manner with increasing liver fat content with an odds ratio of 5.00 (2.63-9.46) in individuals in the highest quartile of liver fat content compared to individuals in the lowest quartile. In genetic analyses, <i>PNPLA3</i> and <i>TM6SF2</i> were both associated with increased risk of NAFLD but not with increased risk of psoriasis.
Conclusion: Observationally, a diagnosis of NAFLD or elevated liver fat content was associated with higher risk of psoriasis. However, using genetic variants as a proxy for NAFLD, we did not find evidence of a causal relationship between NAFLD and psoriasis. Thus, the observational association between NAFLD and psoriasis is presumably a result of shared confounding factors or reverse causation.