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

Budu-Aggrey, A. et al. (2019) Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study. PLoS Medicine, 16(1), e1002739. (doi: 10.1371/journal.pmed.1002739) (PMID:30703100) (PMCID:PMC6354959)

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Background: Psoriasis 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 Findings: Following 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. Conclusions: Our 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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Celis, Dr Carlos and Siebert, Professor Stefan and Ferguson, Dr Lyn and Sattar, Professor Naveed
Creator Roles:
Celis, C.Investigation, Writing – review and editing
Ferguson, L. D.Investigation, Writing – original draft, Writing – review and editing
Siebert, S.Investigation, Writing – review and editing
McInnes, I. B.Investigation, Writing – review and editing
Sattar, N.Conceptualization, Supervision, Writing – review and editing
Authors: Budu-Aggrey, A., Brumpton, B., Tyrrell, J., Watkins, S., Modalsli, E. H., Celis-Morales, C., Ferguson, L. D., Vie, G. Å., Palmer, T., Fritsche, L. G., Løset, M., Nielsen, J. B., Zhou, W., Tsoi, L. C., Wood, A. R., Jones, S. E., Beaumont, R., Saunes, M., Romundstad, P. R., Siebert, S., McInnes, I. B., Elder, J. T., Davey Smith, G., Frayling, T. M., Åsvold, B. O., Brown, S. J., Sattar, N., and Paternoster, L.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Research Centre:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:PLoS Medicine
Publisher:Public Library of Science
ISSN (Online):1549-1676
Copyright Holders:Copyright © 2019 Budu-Aggrey et al.
First Published:First published in PLoS Medicine 16(1): e1002739
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES