Evidence of a causal relationship between body mass index and psoriasis

A mendelian randomization study

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 & 8 others Iain B. McInnes, James T. Elder, George Davey Smith, Timothy M. Frayling, Bjørn Olav Åsvold, Sara J. Brown, Naveed Sattar, Lavinia Paternoster

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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.

Original languageEnglish
Article numbere1002739
Pages (from-to)1-18
Number of pages18
JournalPLoS Medicine
Volume16
Issue number1
DOIs
Publication statusPublished - 31 Jan 2019

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Random Allocation
Psoriasis
Body Mass Index
Mendelian Randomization Analysis
Skin Diseases
Genetic Skin Diseases
Obesity
Odds Ratio
Genome-Wide Association Study
Proxy
Norway
Diagnostic Errors
Single Nucleotide Polymorphism
Meta-Analysis
Life Style

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Budu-Aggrey, A., Brumpton, B., Tyrrell, J., Watkins, S., Modalsli, E. H., Celis-Morales, C., ... Paternoster, L. (2019). Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study. PLoS Medicine, 16(1), 1-18. [e1002739]. https://doi.org/10.1371/journal.pmed.1002739
Budu-Aggrey, Ashley ; Brumpton, Ben ; Tyrrell, Jess ; Watkins, Sarah ; Modalsli, Ellen H. ; Celis-Morales, Carlos ; Ferguson, Lyn D. ; Vie, Gunnhild Åberge ; Palmer, Tom ; Fritsche, Lars G. ; Løset, Mari ; Nielsen, Jonas Bille ; Zhou, Wei ; Tsoi, Lam C. ; Wood, Andrew R. ; Jones, Samuel E. ; Beaumont, Robin ; Saunes, Marit ; Romundstad, Pål Richard ; Siebert, Stefan ; McInnes, Iain B. ; Elder, James T. ; Davey Smith, George ; Frayling, Timothy M. ; Åsvold, Bjørn Olav ; Brown, Sara J. ; Sattar, Naveed ; Paternoster, Lavinia. / Evidence of a causal relationship between body mass index and psoriasis : A mendelian randomization study. In: PLoS Medicine. 2019 ; Vol. 16, No. 1. pp. 1-18.
@article{27c102e4e2664b348f97a25ca8d87a53,
title = "Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization 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-Tr{\o}ndelag 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.",
author = "Ashley Budu-Aggrey and Ben Brumpton and Jess Tyrrell and Sarah Watkins and Modalsli, {Ellen H.} and Carlos Celis-Morales and Ferguson, {Lyn D.} and Vie, {Gunnhild {\AA}berge} and Tom Palmer and Fritsche, {Lars G.} and Mari L{\o}set and Nielsen, {Jonas Bille} and Wei Zhou and Tsoi, {Lam C.} and Wood, {Andrew R.} and Jones, {Samuel E.} and Robin Beaumont and Marit Saunes and Romundstad, {P{\aa}l Richard} and Stefan Siebert and McInnes, {Iain B.} and Elder, {James T.} and {Davey Smith}, George and Frayling, {Timothy M.} and {\AA}svold, {Bj{\o}rn Olav} and Brown, {Sara J.} and Naveed Sattar and Lavinia Paternoster",
note = "funding: AB-A and LP are funded by a grant awarded by the British Skin Foundation (8010 Innovative Project) (http://www.britishskinfoundation.org.uk/). AB-A, LP, SW, and GDS work in a research unit funded by the UK Medical Research Council (MC_UU_00011/1) (https://mrc.ukri.org/). JT is funded by the European Regional Development Fund (ERDF) (http://ec.europa.eu/regional_policy/en/funding/erdf/) and a Diabetes Research and Wellness Foundation fellowship (https://www.drwf.org.uk/). RNB is funded by the Wellcome Trust (https://wellcome.ac.uk/) and Royal Society grant 104150/Z/14/Z (https://royalsociety.org). SEJ is funded by the Medical Research Council (grant MR/M005070/1) (https://mrc.ukri.org/). JT, RNB, and SEJ’s analysis of UK Biobank was under project 9072. TMF and ARW are supported by the European Research Council (grant 323195:GLUCOSEGENES-FP7-IDEAS-ERC) (https://erc.europa.eu/). BB, ML, LGF, and BOA work in a research unit funded by Stiftelsen Kristian Gerhard Jebsen; Faculty of Medicine and Health Sciences, NTNU (https://stiftkgj.no/what-we-do/k-g-jebsen-centres-of-medical-research/?lang=en); The Liaison Committee for education, research and innovation in Central Norway (https://helsemidt.no/helsefaglig/helsefaglig/samarbeidsorganet); and the Joint Research Committee between St. Olav’s Hospital and the Faculty of Medicine and Health Sciences, NTNU (https://www.ntnu.edu/). EHM and ML were supported by a research grant from the Liaison Committee for education, research and innovation in Central Norway (https://helsemidt.no/helsefaglig/helsefaglig/samarbeidsorganet). GAV is supported by a research grant from the Norwegian Research Council, grant number 250335 (https://www.forskningsradet.no/en/Home_page/1177315753906). JBN was supported by grants from the Danish Heart Foundation (https://hjerteforeningen.dk/english/) and the Lundbeck Foundation (https://www.lundbeckfonden.com/en/). SJB holds a Wellcome Trust Senior Research Fellowship in Clinical Science (106865/Z/15/Z) (https://wellcome.ac.uk/). LDF is funded by the British Heart Foundation (BHF) Research Excellence award, grant number RE/13/5/30177 (https://www.bhf.org.uk/for-professionals/information-for-researchers/what-we-fund). The genotyping in HUNT was financed by the National Institutes of Health (NIH) (https://www.nih.gov/); the University of Michigan (https://www.umich.edu/); The Research Council of Norway (https://www.forskningsradet.no/en/Home_page/1177315753906); The Liaison Committee for education, research and innovation in Central Norway (https://helsemidt.no/helsefaglig/helsefaglig/samarbeidsorganet); and the Joint Research Committee between St. Olav’s hospital and the Faculty of Medicine and Health Sciences, NTNU (https://www.ntnu.edu/). The psoriasis meta-GWAS was funded by multiple sources, including the NIH (https://www.nih.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.",
year = "2019",
month = "1",
day = "31",
doi = "10.1371/journal.pmed.1002739",
language = "English",
volume = "16",
pages = "1--18",
journal = "PLoS Medicine",
issn = "1549-1277",
publisher = "Public Library of Science",
number = "1",

}

Budu-Aggrey, A, Brumpton, B, Tyrrell, J, Watkins, S, Modalsli, EH, Celis-Morales, C, Ferguson, LD, Vie, GÅ, Palmer, T, Fritsche, LG, Løset, M, Nielsen, JB, Zhou, W, Tsoi, LC, Wood, AR, Jones, SE, Beaumont, R, Saunes, M, Romundstad, PR, Siebert, S, McInnes, IB, Elder, JT, Davey Smith, G, Frayling, TM, Åsvold, BO, Brown, SJ, Sattar, N & Paternoster, L 2019, 'Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study', PLoS Medicine, vol. 16, no. 1, e1002739, pp. 1-18. https://doi.org/10.1371/journal.pmed.1002739

Evidence of a causal relationship between body mass index and psoriasis : A mendelian randomization study. / Budu-Aggrey, Ashley; Brumpton, Ben; Tyrrell, Jess; Watkins, Sarah; Modalsli, Ellen H.; Celis-Morales, Carlos; Ferguson, Lyn D.; Vie, Gunnhild Åberge; Palmer, Tom; Fritsche, Lars G.; Løset, Mari; Nielsen, Jonas Bille; Zhou, Wei; Tsoi, Lam C.; Wood, Andrew R.; Jones, Samuel E.; Beaumont, Robin; Saunes, Marit; Romundstad, Pål Richard; Siebert, Stefan; McInnes, Iain B.; Elder, James T.; Davey Smith, George; Frayling, Timothy M.; Åsvold, Bjørn Olav; Brown, Sara J.; Sattar, Naveed; Paternoster, Lavinia.

In: PLoS Medicine, Vol. 16, No. 1, e1002739, 31.01.2019, p. 1-18.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evidence of a causal relationship between body mass index and psoriasis

T2 - A mendelian randomization study

AU - Budu-Aggrey, Ashley

AU - Brumpton, Ben

AU - Tyrrell, Jess

AU - Watkins, Sarah

AU - Modalsli, Ellen H.

AU - Celis-Morales, Carlos

AU - Ferguson, Lyn D.

AU - Vie, Gunnhild Åberge

AU - Palmer, Tom

AU - Fritsche, Lars G.

AU - Løset, Mari

AU - Nielsen, Jonas Bille

AU - Zhou, Wei

AU - Tsoi, Lam C.

AU - Wood, Andrew R.

AU - Jones, Samuel E.

AU - Beaumont, Robin

AU - Saunes, Marit

AU - Romundstad, Pål Richard

AU - Siebert, Stefan

AU - McInnes, Iain B.

AU - Elder, James T.

AU - Davey Smith, George

AU - Frayling, Timothy M.

AU - Åsvold, Bjørn Olav

AU - Brown, Sara J.

AU - Sattar, Naveed

AU - Paternoster, Lavinia

N1 - funding: AB-A and LP are funded by a grant awarded by the British Skin Foundation (8010 Innovative Project) (http://www.britishskinfoundation.org.uk/). AB-A, LP, SW, and GDS work in a research unit funded by the UK Medical Research Council (MC_UU_00011/1) (https://mrc.ukri.org/). JT is funded by the European Regional Development Fund (ERDF) (http://ec.europa.eu/regional_policy/en/funding/erdf/) and a Diabetes Research and Wellness Foundation fellowship (https://www.drwf.org.uk/). RNB is funded by the Wellcome Trust (https://wellcome.ac.uk/) and Royal Society grant 104150/Z/14/Z (https://royalsociety.org). SEJ is funded by the Medical Research Council (grant MR/M005070/1) (https://mrc.ukri.org/). JT, RNB, and SEJ’s analysis of UK Biobank was under project 9072. TMF and ARW are supported by the European Research Council (grant 323195:GLUCOSEGENES-FP7-IDEAS-ERC) (https://erc.europa.eu/). BB, ML, LGF, and BOA work in a research unit funded by Stiftelsen Kristian Gerhard Jebsen; Faculty of Medicine and Health Sciences, NTNU (https://stiftkgj.no/what-we-do/k-g-jebsen-centres-of-medical-research/?lang=en); The Liaison Committee for education, research and innovation in Central Norway (https://helsemidt.no/helsefaglig/helsefaglig/samarbeidsorganet); and the Joint Research Committee between St. Olav’s Hospital and the Faculty of Medicine and Health Sciences, NTNU (https://www.ntnu.edu/). EHM and ML were supported by a research grant from the Liaison Committee for education, research and innovation in Central Norway (https://helsemidt.no/helsefaglig/helsefaglig/samarbeidsorganet). GAV is supported by a research grant from the Norwegian Research Council, grant number 250335 (https://www.forskningsradet.no/en/Home_page/1177315753906). JBN was supported by grants from the Danish Heart Foundation (https://hjerteforeningen.dk/english/) and the Lundbeck Foundation (https://www.lundbeckfonden.com/en/). SJB holds a Wellcome Trust Senior Research Fellowship in Clinical Science (106865/Z/15/Z) (https://wellcome.ac.uk/). LDF is funded by the British Heart Foundation (BHF) Research Excellence award, grant number RE/13/5/30177 (https://www.bhf.org.uk/for-professionals/information-for-researchers/what-we-fund). The genotyping in HUNT was financed by the National Institutes of Health (NIH) (https://www.nih.gov/); the University of Michigan (https://www.umich.edu/); The Research Council of Norway (https://www.forskningsradet.no/en/Home_page/1177315753906); The Liaison Committee for education, research and innovation in Central Norway (https://helsemidt.no/helsefaglig/helsefaglig/samarbeidsorganet); and the Joint Research Committee between St. Olav’s hospital and the Faculty of Medicine and Health Sciences, NTNU (https://www.ntnu.edu/). The psoriasis meta-GWAS was funded by multiple sources, including the NIH (https://www.nih.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

PY - 2019/1/31

Y1 - 2019/1/31

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85060952703&partnerID=8YFLogxK

U2 - 10.1371/journal.pmed.1002739

DO - 10.1371/journal.pmed.1002739

M3 - Article

VL - 16

SP - 1

EP - 18

JO - PLoS Medicine

JF - PLoS Medicine

SN - 1549-1277

IS - 1

M1 - e1002739

ER -

Budu-Aggrey A, Brumpton B, Tyrrell J, Watkins S, Modalsli EH, Celis-Morales C et al. Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study. PLoS Medicine. 2019 Jan 31;16(1):1-18. e1002739. https://doi.org/10.1371/journal.pmed.1002739