Common Diseases in Clinical Cohorts - Not Always What They Seem

Area of Science:

• Genomics
• Rare Diseases
• Clinical Diagnostics

Background:

• Misdiagnosis of rare diseases in patients with common conditions delays treatment.
• The impact of rare diseases on common disease diagnosis in research is understudied.

Purpose of the Study:

• To assess the incidence of monogenic rare diseases in patients diagnosed with common conditions.
• To investigate the role of rare diseases in diagnostic challenges for common diseases.

Main Methods:

• Utilized exome and genome sequencing data from UK Biobank and clinical trials.
• Analyzed participants with primary diagnoses of multiple sclerosis, inflammatory bowel disease, and atopic dermatitis.
• Combined genome and transcriptome analyses to understand treatment response.

Main Results:

• Identified 153 participants with rare variants for monogenic disorders across common disease cohorts.
• Observed a 1.12% to 2.86% incidence of rare disease variants in studied common disease populations.
• Replicated findings in independent cohorts and linked molecular diagnosis to therapeutic response.

Conclusions:

• Systematic genome sequencing is valuable for understanding disease heterogeneity and identifying undiagnosed rare diseases.
• Deep molecular phenotyping enhances clinical trials and patient care by revealing rare conditions.
• Highlights the importance of genetic analysis in complex patient cases.