Genomic Risk Score impact on susceptibility to systemic sclerosis

Area of Science:

• Genetics
• Immunology
• Rheumatology

Background:

• Genomic Risk Scores (GRS) are effective in predicting risk for complex traits and immune-mediated inflammatory diseases (IMIDs).
• Systemic sclerosis (SSc) is a complex IMID where early and accurate diagnosis is crucial.

Purpose of the Study:

• To evaluate the performance of GRS in predicting the risk of developing SSc.
• To assess the utility of GRS in differentiating SSc from other IMIDs and its subtypes.

Main Methods:

• Utilized data from the largest SSc Genome-Wide Association Study (GWAS) for allelic effects.
• Developed and validated the best-fitting GRS in an independent cohort.
• Generated subtype-specific GRS and integrated GRS with demographic and immunological parameters.

Main Results:

• The SSc GRS, comprising 33 SNPs, distinguished SSc patients from controls (AUC=0.673) and other IMIDs.
• Combining GRS with age and immune cell counts improved discrimination (AUC=0.787).
• A serological subtype GRS showed moderate performance in differentiating SSc subtypes (AUC=0.693).

Conclusions:

• GRS is successfully implemented for SSc risk prediction.
• GRS shows potential for supporting early and differential diagnosis of SSc.
• Further research may refine GRS for SSc subtype classification.