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ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutrition and Metabolism
Volume 11 - 2024 |
doi: 10.3389/fnut.2024.1451112
Exploring Genetic Associations between Metabolites and Atopic Dermatitis: Insights from Bidirectional Mendelian Randomization Analysis in European Population
Provisionally accepted- 1 Affiliated Calmette Hospital of Kunming Medical University/Kunming First People's Hospital, Kunming, Yunnan Province, China
- 2 Southern Medical University, Guangzhou, Guangdong, China
- 3 Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
Abstract Background: There is growing evidence indicating a complex interaction between blood metabolites and atopic dermatitis (AD). The objective of this study was to investigate and quantify the potential influence of plasma metabolites on atopic dermatitis AD through Mendelian randomization (MR) analysis. Methods: Our procedures followed these steps: instrument variable selection, primary analysis, replication analysis, Meta-analysis of results, reverse MR analysis, and multivariate MR (MVMR) analysis. In our study, the exposure factors were derived from the Canadian Longitudinal Study on Aging (CLSA), encompassing 8,299 individuals of European descent and identifying 1,091 plasma metabolites and 309 metabolite ratios. In primary analysis, AD data, was sourced from the GWAS catalog (Accession ID: GCST90244787), comprising 60,653 cases and 804,329 controls. For replication, AD data from the Finnish R10 database included 15,208 cases and 367,046 controls. We primarily utilized the inverse variance weighting method to assess the causal relationship between blood metabolites and AD. Results: Our study identified significant causal relationships between nine genetically predicted blood metabolites and AD. Specifically, 1-palmitoyl-2-stearoyl-GPC (16:0/18:0) (OR = 0.92, 95% CI 0.89-0.94), 1-methylnicotinamide (OR = 0.93, 95% CI 0.89-0.98), linoleoyl-arachidonoyl-glycerol (18:2/20:4) [1]*(OR = 0.94, 95% CI 0.92-0.96), and 1-arachidonoyl-GPC (20:4n6)* (OR = 0.94, 95% CI 0.92-0.96) were associated with a reduced risk of AD. Conversely, phosphate / linoleoyl-arachidonoyl-glycerol (18:2/20:4) [2]* (OR = 1.07, 95% CI 1.04-1.10), docosatrienoate (22:3n3) (OR = 1.07, 95% CI 1.04-1.10), retinol (Vitamin A) / linoleoyl-arachidonoyl-glycerol (18:2/20:4) [2]* (OR = 1.08, 95% CI 1.05-1.11), retinol (Vitamin A) / linoleoyl-arachidonoyl-glycerol (18:2/20:4) [1]* (OR = 1.08, 95% CI 1.05-1.12), and phosphate / linoleoyl-arachidonoyl-glycerol (18:2/20:4) [1]* (OR = 1.09, 95% CI 1.07-1.12) were associated with an increased risk of AD. No evidence of reverse causality was found in the previously significant results. MVMR analysis further confirmed that 1-palmitoyl-2-stearoyl-GPC (16:0/18:0) and 1-methylnicotinamide are independent and dominant contributors to the development of AD. Conclusions: Our study revealed a causal relationship between genetically predicted blood metabolites andAD. This discovery offers specific targets for drug development in the treatment of AD patients and provides valuable insights for investigating the underlying mechanisms of AD in future research.
Keywords: atopic dermatitis, Blood metabolites, Genome-Wide Association Study, Mendelian randomization, causal inference
Received: 18 Jun 2024; Accepted: 30 Jul 2024.
Copyright: © 2024 He, Hong, Zhao, Li, Xu, Xu, Jing, Ma, Gong, Yang, Zhou, Zheng and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xian Zhao, Affiliated Calmette Hospital of Kunming Medical University/Kunming First People's Hospital, Kunming, Yunnan Province, China
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