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Causal Relationship and Shared Genetic Loci between Psoriasis and Type 2 Diabetes through Trans-Disease Meta-Analysis.

Authors
  • Patrick, Matthew T1
  • Stuart, Philip E1
  • Zhang, Haihan2
  • Zhao, Qingyuan3
  • Yin, Xianyong4
  • He, Kevin4
  • Zhou, Xu-Jie5
  • Mehta, Nehal N6
  • Voorhees, John J1
  • Boehnke, Michael4
  • Gudjonsson, Johann E1
  • Nair, Rajan P1
  • Handelman, Samuel K7
  • Elder, James T8
  • Liu, Dajiang J9
  • Tsoi, Lam C10
  • 1 Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
  • 2 Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
  • 3 Statistical Laboratory, Centre for Mathematical Sciences, University of Cambridge, Cambridge, United Kingdom. , (United Kingdom)
  • 4 Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
  • 5 Renal Division, Peking University First Hospital, Beijing, China. , (China)
  • 6 National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • 7 Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
  • 8 Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA; Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan, USA.
  • 9 Department of Public Health Sciences, Pennsylvania State University College of Medicine, Pennsylvania, USA.
  • 10 Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor Michigan, USA. Electronic address: [email protected]
Type
Published Article
Journal
Journal of Investigative Dermatology
Publisher
Elsevier
Publication Date
Jun 01, 2021
Volume
141
Issue
6
Pages
1493–1502
Identifiers
DOI: 10.1016/j.jid.2020.11.025
PMID: 33385400
Source
Medline
Language
English
License
Unknown

Abstract

Psoriasis and type 2 diabetes (T2D) are complex conditions with significant impacts on health. Patients with psoriasis have a higher risk of T2D (∼1.5 OR) and vice versa, controlling for body mass index; yet, there has been a limited study comparing their genetic architecture. We hypothesized that there are shared genetic components between psoriasis and T2D. Trans-disease meta-analysis was applied to 8,016,731 well-imputed genetic markers from large-scale meta-analyses of psoriasis (11,024 cases and 16,336 controls) and T2D (74,124 cases and 824,006 controls), adjusted for body mass index. We confirmed our findings in a hospital-based study (42,112 patients) and tested for causal relationships with multivariable Mendelian randomization. Mendelian randomization identified a causal relationship between psoriasis and T2D (P = 1.6 × 10‒4, OR = 1.01) and highlighted the impact of body mass index. Trans-disease meta-analysis further revealed four genome-wide significant loci (P < 5 × 10‒8) with evidence of colocalization and shared directions of effect between psoriasis and T2D not present in body mass index. The proteins coded by genes in these loci (ACTR2, ERLIN1, TRMT112, and BECN1) are connected through NF-κB signaling. Our results provide insight into the immunological components that connect immune-mediated skin conditions and metabolic diseases, independent of confounding factors. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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