Shared Genetic Risk and Pathways Between Asthma and Celiac Disease

Garnet Eister; Hui-Qi Qu; Hakon Hakonarson

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Shared Genetic Risk and Pathways Between Asthma and Celiac Disease

Garnet Eister

^*,

Hui-Qi Qu

Hakon Hakonarson

¹ The Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
² Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
³ Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
⁴ Division of Pulmonary Medicine, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
⁵ Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.

Academic Editor: Giuseppe Cappellano

Published: 09 May 2025 by MDPI in The 3rd International Electronic Conference on Biomedicines session Immune System, Tumor Immunology and Autoimmune Disease

Abstract:

Introduction: Asthma has a strong allergic component, while Celiac Disease (CD) is an autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals. This study investigates whether asthma and CD share genetic risk factors, offering insights into their biological interplay and overlapping pathways.

Methods: Pediatric patients diagnosed with asthma (n = 4848) or CD (n = 346) were compared to controls who had never been diagnosed of any allergic or autoimmune diseases (n = 1,963). Ninety-eight patients were diagnosed with both diseases. Asthma (PGS002727) and CD (PGS002067) polygenic risk scores (PRSs) were analyzed separately for females and males. All participants were of European ancestry and recruited by the Center for Applied Genomics (CAG) at the Children’s Hospital of Philadelphia (CHOP).

Results: We conducted a cross-examination, excluding patients diagnosed with both asthma and CD to avoid potential confounding effects. Key findings are as follows:

Female Asthma Patients: Increased asthma PRS (P=2.37E-05) and CD PRS (P=0.018).
Female CD Patients: Elevated asthma PRS (P=0.007) and CD PRS (P=1.04E-25).
Male Asthma Patients: Increased asthma PRS (P=4.77E-04); CD PRS not significant (P=0.420).
Male CD Patients: Higher asthma PRS (P=9.83E-06) and CD PRS (P=4.31E-16).
Controls: Asthma and CD PRS correlated significantly (females: r=0.249, P=6.39E-15; males: r=0.232, P=8.56E-14).

Pathway PRS analyses using ImmuneSigDB C7 (5219 gene sets) showed 630 significantly altered pathway CD PRSs after Bonferroni correction. Pathway PRS associations for asthma were less pronounced. Two pathways identified in CD patients were also increased in asthma patients (P < 0.001 in both sexes): [THAKAR_PBMC_INACTIVATED_INFLUENZA_AGE_21_30YO_RESPONDERS_28DY_DN] and [GSE3039_CD4_TCELL_VS_B1_BCELL_UP].

Conclusions: Our findings highlight a shared genetic risk between asthma and CD. Two shared gene sets related to altered PBMC activity and CD4+ T cells were identified. These findings provide valuable insights into these overlapping mechanisms and identify targets for therapeutic interventions.

Keywords: asthma; celiac disease; polygenic risk score; pathway PRS

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Garnet Eister

Hui-Qi Qu

Hakon Hakonarson