Genetic interrogation for sequence and copy number variants in systemic lupus erythematosus

Area of Science:

• Genetics
• Immunology
• Autoimmune Diseases

Background:

• Early-onset systemic lupus erythematosus (SLE) is characterized by disease severity and a significant genetic contribution.
• Genetic disparities in SLE are pronounced across different ancestries, including Black, Asian, and Hispanic populations.
• Next-generation sequencing (NGS) technologies are crucial for identifying genetic variants linked to autoimmune diseases like SLE.

Purpose of the Study:

• To review known causal variants in polygenic and monogenic forms of SLE.
• To discuss the implications of genetic disparities in SLE pathogenesis and presentation.
• To propose an age-based sequencing strategy for improved clinical diagnostics and patient management.

Main Methods:

• Comprehensive literature review of genetic studies in SLE.
• Analysis of whole exome sequencing (WES) data and other genomic interrogation techniques.
• Synthesis of findings on genetic variants, ancestry, and disease presentation.

Main Results:

• Identification of specific causal variants associated with polygenic and monogenic SLE.
• Elucidation of how genetic factors contribute to disease severity and ancestry-related differences.
• Highlighting the role of genetic burden in early-onset SLE.

Conclusions:

• Genetic factors play a critical role in the development and severity of early-onset SLE, with notable ancestral variations.
• An age-based sequencing approach could enhance diagnostic accuracy and personalize patient management strategies for SLE.
• Further research into genetic disparities is essential for advancing SLE care and treatment.