Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures

Manja Koch¹, Hansjörg Baurecht², Janina S Ried³, Elke Rodriguez², Sabrina Schlesinger¹, Natalie Volks², Christian Gieger⁴, Ina-Maria Rückert⁵, Luise Heinrich⁶, Christina Willenborg⁷, Catherine Smith⁸, Annette Peters⁵, Barbara Thorand⁵, Wolfgang Koenig⁹, Claudia Lamina¹⁰, Henning Jansen¹¹, Florian Kronenberg¹⁰, Jochen Seissler¹², Joachim Thiery¹³, Wolfgang Rathmann¹⁴, Heribert Schunkert¹¹, Jeanette Erdmann⁷, Jonathan Barker⁸, Rajan P Nair¹⁵, Lam C Tsoi¹⁶, James T Elder¹⁷, Ulrich Mrowietz², Michael Weichenthal², Sören Mucha¹⁸, Stefan Schreiber¹⁹, Andre Franke¹⁸, Jochen Schmitt²⁰, Wolfgang Lieb²¹, Stephan Weidinger²²

Affiliations

¹ Institute of Epidemiology, Christian-Albrechts University Kiel, Kiel, Germany.
² Department of Dermatology, Allergology, and Venerology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
³ Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁴ Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁵ Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁶ Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
⁷ Institute for Integrative und Experimental Genomics and DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
⁸ St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Kings College London, London, UK.
⁹ Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany.
¹⁰ Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
¹¹ Deutsches Herzzentrum Munich, Technische Universität Munich, Munich, Germany.
¹² Medizinische Klinik und Poliklinik IV, Diabetes Zentrum, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany.
¹³ Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
¹⁴ German Diabetes Center, Leibniz Institute at Heinrich Heine University Düsseldorf, Institute of Biometrics and Epidemiology, Düsseldorf, Germany.
¹⁵ Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
¹⁶ Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
¹⁷ Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA; Ann-Arbor Veteran Affairs Hospital, Ann Arbor, Michigan, USA.
¹⁸ Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
¹⁹ Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany.
²⁰ Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany; These authors contributed equally to this work.
²¹ Institute of Epidemiology, Christian-Albrechts University Kiel, Kiel, Germany; These authors contributed equally to this work.
²² Department of Dermatology, Allergology, and Venerology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; These authors contributed equally to this work.. Electronic address: sweidinger@dermatology.uni-kiel.de.

PMID: 25599394
PMCID: PMC4402117
DOI: 10.1038/jid.2015.8

Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures

Manja Koch et al. J Invest Dermatol. 2015 May.

. 2015 May;135(5):1283-1293.

doi: 10.1038/jid.2015.8. Epub 2015 Jan 19.

Authors

Affiliations

¹ Institute of Epidemiology, Christian-Albrechts University Kiel, Kiel, Germany.
² Department of Dermatology, Allergology, and Venerology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
³ Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁴ Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁵ Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁶ Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
⁷ Institute for Integrative und Experimental Genomics and DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
⁸ St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Kings College London, London, UK.
⁹ Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany.
¹⁰ Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
¹¹ Deutsches Herzzentrum Munich, Technische Universität Munich, Munich, Germany.
¹² Medizinische Klinik und Poliklinik IV, Diabetes Zentrum, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany.
¹³ Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
¹⁴ German Diabetes Center, Leibniz Institute at Heinrich Heine University Düsseldorf, Institute of Biometrics and Epidemiology, Düsseldorf, Germany.
¹⁵ Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
¹⁶ Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
¹⁷ Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA; Ann-Arbor Veteran Affairs Hospital, Ann Arbor, Michigan, USA.
¹⁸ Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
¹⁹ Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany.
²⁰ Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany; These authors contributed equally to this work.
²¹ Institute of Epidemiology, Christian-Albrechts University Kiel, Kiel, Germany; These authors contributed equally to this work.
²² Department of Dermatology, Allergology, and Venerology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; These authors contributed equally to this work.. Electronic address: sweidinger@dermatology.uni-kiel.de.

PMID: 25599394
PMCID: PMC4402117
DOI: 10.1038/jid.2015.8

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.

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Conflict of interest statement

Conflict of Interest

JTE reports grants from National Institutes of Health, during the conduct of the study. JSch reports grants from MSD, grants from Wyeth, grants from Novartis, personal fees from Genentech, outside the submitted work. SW reports grants from German Federal Ministry of Education and Research, during the conduct of the study; grants from Pfizer, grants and personal fees from Biogen, grants and personal fees from Novartis, personal fees from Roche-Posay, outside the submitted work. HS reports grants from e:AtherosSysMed, grants from DZHK/MHA, grants from CVgenes@target, personal fees from AstraZeneca Germany, personal fees from AstraZeneca India, personal fees from SERVIER GmbH Germany, personal fees from Boehringer-Ingelheim Germany, personal fees from MSD Sharp & Dohme GmbH Germany, personal fees from AMGEN GmbH Germany, personal fees from BERLIN-CHEMIE AG Germany, outside the submitted work.

Figures

**Figure 1**
Manhattan plot of Metabochip results on psoriasis.

See this image and copyright information in PMC

References

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Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures

Affiliations

Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical