Causal Relationship and Shared Genetic Loci between Psoriasis and Type 2 Diabetes through Trans-Disease Meta-Analysis
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:141 |
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| Enthalten in: |
The Journal of investigative dermatology - 141(2021), 6 vom: 01. Juni, Seite 1493-1502 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Patrick, Matthew T [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 19.11.2021 Date Revised 16.07.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jid.2020.11.025 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM319494330 |
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| 100 | 1 | |a Patrick, Matthew T |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Causal Relationship and Shared Genetic Loci between Psoriasis and Type 2 Diabetes through Trans-Disease Meta-Analysis |
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| 500 | |a Date Revised 16.07.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Meta-Analysis | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 700 | 1 | |a Stuart, Philip E |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Haihan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Qingyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Xianyong |e verfasserin |4 aut | |
| 700 | 1 | |a He, Kevin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Xu-Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Mehta, Nehal N |e verfasserin |4 aut | |
| 700 | 1 | |a Voorhees, John J |e verfasserin |4 aut | |
| 700 | 1 | |a Boehnke, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Gudjonsson, Johann E |e verfasserin |4 aut | |
| 700 | 1 | |a Nair, Rajan P |e verfasserin |4 aut | |
| 700 | 1 | |a Handelman, Samuel K |e verfasserin |4 aut | |
| 700 | 1 | |a Elder, James T |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Dajiang J |e verfasserin |4 aut | |
| 700 | 1 | |a Tsoi, Lam C |e verfasserin |4 aut | |
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