Date Published: January 31, 2019
Publisher: Public Library of Science
Author(s): Ashley Budu-Aggrey, Ben Brumpton, Jess Tyrrell, Sarah Watkins, Ellen H. Modalsli, Carlos Celis-Morales, Lyn D. Ferguson, Gunnhild Åberge Vie, Tom Palmer, Lars G. Fritsche, Mari Løset, Jonas Bille Nielsen, Wei Zhou, Lam C. Tsoi, Andrew R. Wood, Samuel E. Jones, Robin Beaumont, Marit Saunes, Pål Richard Romundstad, Stefan Siebert, Iain B. McInnes, James T. Elder, George Davey Smith, Timothy M. Frayling, Bjørn Olav Åsvold, Sara J. Brown, Naveed Sattar, Lavinia Paternoster, Cathryn Lewis
Abstract: BackgroundPsoriasis is a common inflammatory skin disease that has been reported to be associated with obesity. We aimed to investigate a possible causal relationship between body mass index (BMI) and psoriasis.Methods and findingsFollowing a review of published epidemiological evidence of the association between obesity and psoriasis, mendelian randomization (MR) was used to test for a causal relationship with BMI. We used a genetic instrument comprising 97 single-nucleotide polymorphisms (SNPs) associated with BMI as a proxy for BMI (expected to be much less confounded than measured BMI). One-sample MR was conducted using individual-level data (396,495 individuals) from the UK Biobank and the Nord-Trøndelag Health Study (HUNT), Norway. Two-sample MR was performed with summary-level data (356,926 individuals) from published BMI and psoriasis genome-wide association studies (GWASs). The one-sample and two-sample MR estimates were meta-analysed using a fixed-effect model. To test for a potential reverse causal effect, MR analysis with genetic instruments comprising variants from recent genome-wide analyses for psoriasis were used to test whether genetic risk for this skin disease has a causal effect on BMI.Published observational data showed an association of higher BMI with psoriasis. A mean difference in BMI of 1.26 kg/m2 (95% CI 1.02–1.51) between psoriasis cases and controls was observed in adults, while a 1.55 kg/m2 mean difference (95% CI 1.13–1.98) was observed in children. The observational association was confirmed in UK Biobank and HUNT data sets. Overall, a 1 kg/m2 increase in BMI was associated with 4% higher odds of psoriasis (meta-analysis odds ratio [OR] = 1.04; 95% CI 1.03–1.04; P = 1.73 × 10−60). MR analyses provided evidence that higher BMI causally increases the odds of psoriasis (by 9% per 1 unit increase in BMI; OR = 1.09 (1.06–1.12) per 1 kg/m2; P = 4.67 × 10−9). In contrast, MR estimates gave little support to a possible causal effect of psoriasis genetic risk on BMI (0.004 kg/m2 change in BMI per doubling odds of psoriasis (−0.003 to 0.011). Limitations of our study include possible misreporting of psoriasis by patients, as well as potential misdiagnosis by clinicians. In addition, there is also limited ethnic variation in the cohorts studied.ConclusionsOur study, using genetic variants as instrumental variables for BMI, provides evidence that higher BMI leads to a higher risk of psoriasis. This supports the prioritization of therapies and lifestyle interventions aimed at controlling weight for the prevention or treatment of this common skin disease. Mechanistic studies are required to improve understanding of this relationship.
Partial Text: Psoriasis is a common inflammatory skin disorder that is characterized by erythematous scaly plaques; severe disease is associated with significant impairment in physical and mental health . Psoriasis affects approximately 2% of people within European populations , with higher prevalence estimates in northern regions of Europe . The prevalence of disease has also been found to be increasing .
The rising prevalence of psoriasis and obesity are important public health concerns [3,5,37,45]. We found evidence of increased BMI having a causal effect upon occurrence of psoriasis, and the estimated effect size is of a magnitude that is likely to be clinically significant (9% increased risk of psoriasis for 1 unit increase in BMI). Furthermore, the direction and magnitude of effect seen is notably consistent with that seen observationally and in previous literature. In the reverse direction, the estimate of 0.27 kg/m2 suggests much less influence of psoriasis on an individual’s BMI. Overall, our results give evidence that the observational estimates in the literature are predominantly explained by a causal effect of BMI upon psoriasis and are not substantially impacted by unmeasured confounding, implying that excess adiposity is part of the reason for some individuals developing psoriasis.