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
C2 - 30703100
SN - 1549-1277
VL - 16
SP - 1
EP - 18
JO - PLoS Medicine
JF - PLoS Medicine
IS - 1
M1 - e1002739
ER -
