Mendelian randomization analysis to analyze the genetic causality between different levels of obesity and different allergic diseases

Abstract

Background: The causal relationship between obesity and different allergic diseases remains controversial.

Methods: The Two Sample MR package and Phenoscanner database were used to obtain and filter Genome-Wide Association Study (GWAS) data from the Open GWAS database. Mendelian randomization (MR) analysis was used to study the causal relationship between different levels of obesity and different allergic diseases. The data sets related to obesity and asthma were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened by the limma package. Cluster Profiler and GO plot packages were used for enrichment analysis to verify the results of MR analysis.

Results: Two-sample MR analysis showed a causal relationship between obesity and childhood allergy (age < 16), allergic asthma and atopic dermatitis (P < 0.05). In addition, there was also a causal relationship between allergic asthma and obesity (P < 0.05), while there was no genetic causal relationship between obesity and allergic rhinitis, eczema, lactose intolerance and so on (P > 0.05). Subgroup analysis revealed a causal relationship between both class 1 and class 2 obesity and childhood allergy (age < 16) (P < 0.05). Obesity class 1 was associated with allergic asthma, while obesity class 3 was associated with atopic dermatitis (P < 0.05). Bioinformatics analysis shows that there were common DEGs between obesity and allergic asthma.

Conclusion: Obesity is a risk factor for childhood allergy (age < 16), allergic asthma and atopic dermatitis, while allergic asthma is also a risk factor for obesity. Class 1 and class 2 obesity are both causally associated with childhood allergy (age < 16). In addition, there is a causal relationship between milder obesity and allergic asthma, while heavier obesity is causally related to atopic dermatitis.

Keywords: Allergic asthma; Allergic disease; Causal relationship; Mendelian randomization; Obesity.

Fig. 1

A: The flow chart. B: The word cloud chart

Fig. 2

Forest plot for MR analysis of obesity and different allergic diseases. A: childhood allergy (age < 16). B: allergic asthma. C: allergic rhinitis. D: atopie dermatit is. E: eczema. F: allergic urticaria. G: allergic purpura. H : allergic conjunctivitis. I: lactose intolerance. MR: mendel ian random ization

Fig. 3

Scatter plot for MR analysis of obesity and different allergic diseases. A: childhood allergy (age < 16). B: allcrgic asthma. C: allcrgic rhinitis. 0: atopic dennatitis. E: eczema. f: allergic unicaria. G: allergic purpura. II: allergic conjunctivitis. I : lactose intolerance

Fig. 4

Forest plot and scatter plot for MR analysis of childhood allergy, allergic asthma, atopic dermatitis and obesity. A-B: childhood allergy (age < 16) and obesity. C-D: allergic asthma and obesity. E-F: atopic dermatitis and obesity. MR: mendelian random ization

Fig. 5

Forest plots for MR analysis of different levels of obesity and different allergic diseases. A-C: obesity class I and childhood allergy (age < 16), allergic asthm a, atopic dennatitis. D-F: obesity class 2 and childhood allergy (age < 16), allergic asthma, atopic dermatitis. G-1: obesity class 3 and childhood allergy (age < 16), allergic asthma, atopic dermatitis

Fig. 6

Scatter plots for MR analysis of different levels of obesity and different allergic diseases. A -C: obesity class I and childhood allergy (age < 16). allergic asthma. atopic dermatitis. D-F: obesity class 2 and childhood allergy (age < 16), allergic asthma. atopic dermatitis. G-1:obesity class 3 and childhood allergy (age < 16). allergic asthma, atopic dermatitis

Fig. 7

Bioinfonnatic Analysis. A-B: Volcano map and heat map of obesity-associated DEGs. C-D: Volcano map and heat map of asthma-associated DEGs. E : Venn diagram of DEGs common to obesity and asthma. F-G: GO-KEGG enrichment analysis of DEGs. DEGs: differentially expressed genes; GO: Gene Ontology; KEGG : Kyoto Encyclopedia of Genes and Genomes