Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study

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.

Relationship of Visceral Fat and Adipokines with Cardiometabolic Diseases in Psoriasis

“…This case-control study, in which clinical and metabolic parameters, body fat distribution and biomarkers of inflammation were measured simultaneously in a single cohort of patients with psoriasis, found that visceral fat was an independent predictor of psoriasis and that the effect of visceral fat was mediated by the pro-inflammatory cytokine IL-6. A recent study has shown evidence to suggest a causal relationship between a high BMI and psoriasis risk (24). It has also been demonstrated that visceral fat was increased in patients with psoriasis (16), and circulating IL-6 levels have been found to be elevated in psoriasis in 2 previous studies (25,26).…”

Obesity Is a Risk Factor for Severe COVID-19 Infection

“…Obesity per se is an independent and causal risk factor for the development of immune mediated disease e.g. psoriasis, 4 suggesting that such adipose state may have systemic immune consequence upon additional environmental provocation. In terms of host defense, Downloaded from http://ahajournals.org by on June 9, 2020 obesity impairs adaptive immune responses to influenza virus, 5 and conceivably could do so in COVID-19.…”

Research Techniques Made Simple: Using Genetic Variants for Randomization

“…Additionally, combining individual variants into a genetic risk score increases the instrument strength. The instrument for BMI in our psoriasis analysis had an F-statistic of 7,091, indicating a strong instrument for BMI (Budu-Aggrey et al, 2019).…”