GWAS and EWAS in Patients With Erdheim-Chester Disease

Genome-wide Association Study (GWAS) and Epigenome-wide Association Study (EWAS) in Patients With Erdheim-Chester Disease

Erdheim-Chester Disease (ECD) is a rare form of histiocytosis characterized by the proliferation of blood cells, known as histiocytes, which infiltrate various organs and tissues, often causing irreversible damage. The causes of the condition are still unknown, and although some mutations in genes involved in cell proliferation have been identified, other factors may be involved. Susceptibility to developing rare diseases like ECD is typically associated with genetic factors, including DNA polymorphisms and epigenetic modifications.

This study aims to analyze the entire genome of a large cohort of patients with ECD and healthy controls to determine whether there are polymorphisms and epigenetic variants associated with susceptibility to developing the disease. The study could thus clarify the genetic predisposition to ECD development, provide insights into disease pathogenic mechanisms, and identify proteins or cellular mechanisms potentially targeted by specific treatments.

Study Overview

• Status: Recruiting
• Conditions: Erdheim-Chester Disease
• Intervention / Treatment: Genetic: Presence of polymorphisms

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Augusto Vaglio; Phone Number: 3200026532; Email: augusto.vaglio@meyer.it

Study Locations

• France
  • Paris, France
    • Recruiting
    • Hôpital Pitié Salpêtrière
    • Contact: Julien Haroche
• Italy
  • Florence, Italy
    • Recruiting
    • Meyer Children's Hospital IRCCS
    • Contact: Augusto Vaglio; Email: augusto.vaglio@meyer.it
  • Milano, Italy
    • Recruiting
    • IRCCS Ospedale San Raffaele
    • Contact: Lorenzo Dagna
  • Parma, Italy
    • Recruiting
    • AOU Parma
    • Contact: Davide Martorana
• Spain
  • Granada, Spain
    • Recruiting
    • Genetics Lab, CSIC
    • Contact: Javier Martin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Incident and prevalent patients with ECD

Description

Inclusion Criteria:

- ECD with histological confirmation of disease

Exclusion criteria:

- previously treated patients (for methylation and gene expression)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Presence of polymorphisms; Statistical analysis of GWAS data, Genome-wide methylation pattern analysis, Integration of GWAS data and methylation data (meQTL analysis), Pathway enrichment analysis	Genetic: Presence of polymorphisms; Statistical analysis of GWAS data, Genome-wide methylation pattern analysis, Integration of GWAS data and methylation data (meQTL analysis), Pathway enrichment analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Polymorphisms and genetic variants correlated with disease development	To investigate the presence of polymorphisms and genetic variants correlated with disease development, through a GWAS study. This task will be carried out by analyzing the frequency of the identified polymorphisms in patients and controls	5 years
Methylation in Erdheim-Chester disease	To identify differences in gene methylation between patients with ECD and healthy controls, through an EWAS study. This task will be carried out by analyzing the grade of methylation in patients and controls	5 years
Gene expression in Erdheim-Chester disease	To investigate the correlation between genetic variants or epigenetic profiles associated with the disease (previous outcomes) and specific clinical manifestations (organ involvement, somatic mutations, response to treatment, survival)	5 years

Collaborators and Investigators

• Sponsor: Augusto Vaglio

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2019
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: February 21, 2024
• First Submitted That Met QC Criteria: March 18, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Erdheim-Chester Disease
• Other Study ID Numbers: ECDGWAS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No