Implementation of an integrated network analysis strategy for multi-omics data: Application to GWAS data of allergic diseases and EWAS data of IgE levels
Authors/Creators
- 1. Group of Genomic Epidemiology and Multifactorial Diseases, Université Paris Cité, Inserm, UMRS-1124, Paris, France
Description
Motivation: Both genetic and epigenetic mechanisms influence the risk of allergic diseases (AD) and Immunoglobulin E (IgE) levels, a key intermediate phenotype in allergy. Integration of omics data related to AD and IgE can provide more insight into allergy-related mechanisms.
Methodology: We applied network analysis to summary-level data from a publicly available genome-wide association study (GWAS) of AD (242,569 subjects, GWAS catalog: GCST005038), and from epigenome-wide association studies (EWAS) of IgE levels based on targeted bisulfite sequencing and conducted separately in 343 asthmatics and 370 non-asthmatics from the EGEA study. We used the STRING protein-protein interaction network as background and the SigMod method to identify modules (sub-networks) enriched in trait-associated genes. We then investigated the relationships between the AD-GWAS gene module and each of the two IgE-EWAS gene modules.
Results: We identified three modules of (i) 292 genes and 1,233 interactions derived from AD-GWAS; (ii) 251 genes and 720 interactions derived from IgE-EWAS in asthmatics; (iii) 205 genes and 534 interactions derived from IgE-EWAS in non-asthmatics. More than 99% of the genes from each module were nominally associated (P≤0.05) with their respective trait. The AD-GWAS module shared eight and seven genes, respectively, with IgE-EWAS modules (asthmatics and non-asthmatics). A significant proportion of AD-GWAS module genes directly interacted with genes from each IgE-EWAS module (more than 70%, P<10-5). Enrichment analysis of the genes belonging to each of the two AD-GWAS and IgE-EWAS joint modules revealed a high proportion of shared pathways, including Interferon gamma signaling, pathways related to antigen presentation in the context of MHC complex, PD-1 signaling, Co-stimulation by the CD20 family, and Signaling by interleukins. This study shows shared biological mechanisms underlying AD-GWAS and IgE-EWAS gene modules and better insight into the biological mechanisms underlying the risk of allergic diseases and the regulation of IgE production.