Psoriasis and cardiometabolic traits: Modest association but distinct genetic architectures

Manja Koch, Hansjörg Baurecht, Janina S. Ried, Elke Rodriguez, Sabrina Schlesinger, Natalie Volks, Christian Gieger, Ina Maria Rückert, Luise Heinrich, Christina Willenborg, Catherine Smith, Annette Peters, Barbara Thorand, Wolfgang Koenig, Claudia Lamina, Henning Jansen, Florian Kronenberg, Jochen Seissler, Joachim Thiery, Wolfgang RathmannHeribert Schunkert, Jeanette Erdmann, Jonathan Barker, Rajan P. Nair, Lam C. Tsoi, James T. Elder, Ulrich Mrowietz, Michael Weichenthal, Sören Mucha, Stefan Schreiber, Andre Franke, Jochen Schmitt, Wolfgang Lieb, Stephan Weidinger*

*Corresponding author for this work

Abstract

Psoriasis has been linked to cardiometabolic diseases, but epidemiological findings are inconsistent. We investigated the association between psoriasis and cardiometabolic outcomes in a German cross-sectional study (n=4,185) and a prospective cohort of German Health Insurance beneficiaries (n=1,811,098). A potential genetic overlap was explored using genome-wide data from >22,000 coronary artery disease and >4,000 psoriasis cases, and with a dense genotyping study of cardiometabolic risk loci on 927 psoriasis cases and 3,717 controls. After controlling for major confounders, in the cross-sectional analysis psoriasis was significantly associated with type 2 diabetes (T2D, adjusted odds ratio (OR)=2.36; 95% confidence interval CI=1.26-4.41) and myocardial infarction (MI, OR=2.26; 95% CI=1.03-4.96). In the longitudinal study, psoriasis slightly increased the risk for incident T2D (adjusted relative risk (RR)=1.11; 95% CI=1.08-1.14) and MI (RR=1.14; 95% CI=1.06-1.22), with highest risk increments in systemically treated psoriasis, which accounted for 11 and 17 excess cases of T2D and MI per 10,000 person-years. Except for weak signals from within the major histocompatibility complex, there was no evidence of genetic risk loci shared between psoriasis and cardiometabolic traits. Our findings suggest that psoriasis, in particular severe psoriasis, increases the risk for T2D and MI, and that the genetic architecture of psoriasis and cardiometabolic traits is largely distinct.

Original languageEnglish
JournalJournal of Investigative Dermatology
Volume135
Issue number5
Pages (from-to)1283-1293
Number of pages11
ISSN0022-202X
DOIs
Publication statusPublished - 22.05.2015

Funding

We thank all individuals with psoriasis and CAD, their families, control individuals, and clinicians for their participation. The KORA study was initiated and financed by the Helmholtz Zentrum München—German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria. The project received infrastructure support through the DFG Clusters of Excellence “Inflammation at Interfaces” (grants EXC306 and EXC306/2), and was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (e:AtheroSysMed and sysINFLAME, grant 01ZX1306A) and the PopGen 2.0 network (01EY1103). Support for the case-control psoriasis sample used for this study was provided by the National Institutes of Health (R01AR042742, R01AR050511, R01AR054966, R01AR062382, and R01AR065183 to JTE). JTE is supported by the Ann Arbor Veterans Affairs Hospital. This study makes use of data generated by the CARDIoGRAM Consortium and the Wellcome Trust Case-Control Consortium. Members of the consortia are listed in the Data Supplement. A full list of the Wellcome Trust Case-Control Consortium investigators who contributed to the generation of the data is available from www.wtccc.org.uk . Funding for the project was provided by the Wellcome Trust under award 076113 and 085475. We also acknowledge support from the Department of Health via the NIHR BioResource Clinical Research Facility and comprehensive Biomedical Research Centre award to Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. The funders had no role in the study design, in the collection, analysis, and interpretation of data, in the writing of the manuscript, and in the decision to submit the article for publication.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being
  2. SDG 5 - Gender Equality
    SDG 5 Gender Equality

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