Bidirectional Mendelian Randomization identifies plasma proteins associated with urticaria risk

Area of Science:

• Genetics
• Immunology
• Proteomics

Background:

• Urticaria is a common autoimmune skin condition causing wheals and itching, impacting quality of life.
• Previous studies suggested plasma proteins' role in urticaria, but lacked causal evidence.
• A Mendelian randomization study is needed to establish causal links between plasma proteins and urticaria.

Purpose of the Study:

• To investigate the causal relationship between plasma protein levels and the risk of developing urticaria.
• To identify specific plasma proteins that act as protective or risk factors for urticaria.
• To explore potential bidirectional causal links between plasma proteins and urticaria.

Main Methods:

• A two-sample, bidirectional Mendelian randomization study was performed.
• Genome-wide association study data for 4907 plasma proteins and urticaria were analyzed.
• Statistical tests (Cochran's Q, MR-Egger, MR-PRESSO) assessed heterogeneity and pleiotropy; sensitivity analyses were conducted.

Main Results:

• Significant associations were found between 4907 plasma proteins and urticaria risk.
• Protective factors identified: GZMB, MICB, FTMT.
• Risk factors identified: CHCHD10, HBB, LILRB2, IL21, JPH4, ISOC1.
• A bidirectional causal relationship was found between ISOC1 and urticaria.

Conclusions:

• This study establishes causal relationships between specific plasma protein phenotypes and urticaria.
• Findings provide valuable insights into urticaria pathophysiology.
• Identified proteins may serve as potential therapeutic targets for urticaria treatment.