Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 141, Issue 6, Pages 1493-1502Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2020.11.025
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Funding
- Arthritis National Research Foundation
- National Psoriasis Foundation
- National Institutes of Health [R01AR042742, R01AR050511, R01AR054966, R01AR063611, R01AR065183, K01AR072129, DK062370]
- Dermatology Foundation
- Precision Health Scholars Award from the University of Michigan
- Dawn and Dudley Holmes Foundation
- Babcock Memorial Trust
- Doris Duke Foundation [2013106]
- National Institute of Health [K08AR060802, R01AR06907]
- Taubman Medical Research Institute as the Frances and Kenneth Eisenberg Emerging Scholar
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [UM-SBDRC 1P30AR075043]
- National Psoriasis Founadtion Psoriasis Prevention Initiative
- Taubman Institute Innovation Project
- Ann Arbor Veterans Affairs Hospital
- Beijing Natural Science Foundation [Z190023]
- University of Michigan Health SystemPeking University Health Science Center Joint Institute for Translational and Clinical Research [BMU2017JI007]
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Psoriasis and type 2 diabetes share genetic components, with a causal relationship confirmed through Mendelian randomization. Trans-disease meta-analysis identified four genome-wide significant loci and revealed shared mechanisms between the two conditions.
Psoriasis and type 2 diabetes (T2D) are complex conditions with significant impacts on health. Patients with psoriasis have a higher risk of T2D (similar to 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 x 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 x 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-KB signaling. Our results provide insight into the immunological components that connect immune-mediated skin conditions and metabolic diseases, independent of confounding factors.
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