Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study
Year: 2019
Type: article
Study design: Observational Study
Abstract: 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.
Source: PLoS Medicine
Authors: 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
Institutions: University of Bristol, MRC Integrative Epidemiology Unit, Medical Research Council, Norwegian University of Science and Technology, St Olav's University Hospital, University of Exeter, Royal Devon and Exeter Hospital, University of Glasgow, Lancaster University, University of Michigan, Michigan Medicine, VA Ann Arbor Healthcare System, Ann Arbor VA Medical Center, University of Dundee, Ninewells Hospital
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,000
Funders: American Academy of Allergy Asthma and Immunology, Eli Lilly and Company, Pfizer, Celgene, University of Michigan, Hjerteforeningen, Norges Teknisk-Naturvitenskapelige Universitet, Wellcome Trust, Diabetes Research and Wellness Foundation, British Heart Foundation, Royal Society, British Skin Foundation, British Association of Dermatologists, Academy of Medical Sciences, University of Bristol, Lundbeckfonden, Helse Midt-Norge, Norges Forskningsråd, National Institutes of Health, College of Pharmacy, University of Michigan, Fakultet for medisin og helsevitenskap, Norges Teknisk-Naturvitenskapelige Universitet, Medical Research Council, European Regional Development Fund, Faculty of Medicine and Health, University of Sydney, Norwegian Institute of Public Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources, FP7 Ideas: European Research Council
Awards: G1058688197, The causes of hyperglycaemia in the face of rising obesity, G228966285, G2291477964, Molecular mechanisms in atopic skin., Identifying non-coding mutations in early-onset diabetes, G2530512575, G2863306651, Linkage Analysis of Familial Psoriasis, Using genetics to understand how the maternal intrauterine environment influences fetal growth., G4503628494, The genetics of favourable adiposity, Functional Genomics of Psoriasis, G5850737185, Mendelian randomization to hypothesis-free causal inference, G6868616705, Research Excellence, Genetic and Genomic Dissection of Psoriatic Arthritis, G7990456425, General Clinical Research Center, G9000268495
OpenAlex ID: W2913651502