Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study.
<h4>Background</h4>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.<h4>Methods and findings</h4>Following a review of publi...
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doaj-f74e86d2e0074e57ac87d4c412e76f842021-04-21T22:50:46ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762019-01-01161e100273910.1371/journal.pmed.1002739Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study.Ashley Budu-AggreyBen BrumptonJess TyrrellSarah WatkinsEllen H ModalsliCarlos Celis-MoralesLyn D FergusonGunnhild Åberge VieTom PalmerLars G FritscheMari LøsetJonas Bille NielsenWei ZhouLam C TsoiAndrew R WoodSamuel E JonesRobin BeaumontMarit SaunesPål Richard RomundstadStefan SiebertIain B McInnesJames T ElderGeorge Davey SmithTimothy M FraylingBjørn Olav ÅsvoldSara J BrownNaveed SattarLavinia Paternoster<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pmed.1002739 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study. PLoS Medicine |
author_facet |
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 |
author_sort |
Ashley Budu-Aggrey |
title |
Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study. |
title_short |
Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study. |
title_full |
Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study. |
title_fullStr |
Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study. |
title_full_unstemmed |
Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study. |
title_sort |
evidence of a causal relationship between body mass index and psoriasis: a mendelian randomization study. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Medicine |
issn |
1549-1277 1549-1676 |
publishDate |
2019-01-01 |
description |
<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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. |
url |
https://doi.org/10.1371/journal.pmed.1002739 |
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