Celiac disease (CD) is a complex, immune-mediated disorder triggered by gluten ingestion in genetically predisposed individuals.

While advances in HLA genotyping have transformed risk assessment and diagnosis, a substantial proportion of heritability remains unexplained, and environmental triggers contributing to disease onset and progression are only partially understood. Furthermore, epidemiological shifts highlight the need to investigate both established and emerging risk factors within diverse populations and environments. Recent multi-omics profiling, genome-wide association studies (GWAS), and exposomics have uncovered promising new genetic loci, epigenetic signatures, and environmental exposures as potential contributors to Celiac Disease susceptibility and phenotypic variability. Hypotheses about the gut microbiome, early-life infections, dietary patterns, and chemical exposures are gaining attention, yet findings are often disparate and require rigorous validation and cross-disciplinary integration.

This Research Topic is dedicated to the next generation of genetic and environmental risk factors that shape the landscape of celiac disease. Our aim is to identify novel biomarkers for early and accurate diagnosis, and elucidate the global epidemiological patterns of Celiac Disease.

Despite progress, significant challenges remain, including:
- A gap in integration between large-scale genetic data and practical biomarker development.
- Limited understanding of gene-environment interactions that influence disease onset and response to gluten exposure.
- Major variability in Celiac Disease prevalence and presentation across ethnicities, geographical locations, and age groups—suggesting additional, yet-undiscovered, modifiers.
- Under-recognition of non-classical, extraintestinal, and seronegative forms of Celiac Disease, particularly in under-resourced settings.

The main goal is to identify previously unrecognized genetic determinants and molecular signatures associated with Celiac Disease susceptibility, progression, and heterogeneity. Investigate specific environmental risk factors—such as microbiome dynamics, viral agents, early dietary exposures, pollutants, and urbanization. Characterize gene-environment interactions that modulate disease risk and clinical outcomes. As well, to improve early detection and stratification, especially in high-risk and non-classic cases, through novel biomarkers and integrative diagnostic models and to map global and regional trends in Celiac Disease prevalence, informing public health strategies and personalized prevention.

We welcome submissions—including original research, reviews, systematic reviews, and case reports—focusing on the following areas:

- Novel Genetic Markers: GWAS, next-generation sequencing, and polygenic risk score studies identifying previously uncharacterized susceptibility genes and their functional consequences.
- Environmental Triggers: Investigations into the role of infections, diet (beyond gluten), antibiotic exposures, microbiome alterations, and environmental chemicals.
- Gene-Environment Interactions: Multi-omics and systems biology approaches elucidating interactions that drive disease risk or modify phenotype.
- Biomarker Discovery: Identification and validation of serological, genetic or microbiome-based biomarkers to enable earlier and more precise diagnosis.
- Epidemiological Trends: Large-scale and cross-ethnic studies mapping Celiac Disease prevalence, age of onset, clinical presentation, and diagnostic disparities.
- Non-classical and Extraintestinal Presentations: Research focused on atypical, silent, and seronegative Celiac Disease, especially as they relate to genetic and environmental variability.
- Interdisciplinary and Translational Studies: Efforts bridging laboratory discoveries with clinical practice, public health policy, and patient-centered care.

Are you interested in contributing a manuscript to this Research Topic?

New Genetic and Environmental Risk Factors in Celiac Disease: Advancing Diagnosis, Pathophysiology, and Epidemiology

Topic Coordinator