Causal Relationship Between Sjögren's Syndrome and Atherosclerosis: A Bidirectional, Two-Sample, Mendelian...

Area of Science:

• Immunology
• Cardiovascular Medicine
• Genetics

Background:

• Sjögren's syndrome (SS) and atherosclerosis (AS) share inflammatory pathways.
• Observational studies suggest a link between SS and increased AS risk, but causality is unclear.
• This study investigates bidirectional causality between SS and coronary, cerebral, and peripheral AS using Mendelian randomization.

Purpose of the Study:

• To determine if SS causally influences the risk of developing different types of AS.
• To investigate if AS causally influences the risk of developing SS.
• To explore the bidirectional genetic relationship between SS and AS subtypes.

Main Methods:

• Utilized Mendelian randomization (MR) with genetic variants from large genome-wide association studies (GWAS).
• Employed inverse-variance weighted (IVW) as the primary method, supplemented by weighted median, MR-Egger, and mode-based methods.
• Assessed pleiotropy and result stability using Cochran's Q, MR-Egger intercept, MR-PRESSO, and leave-one-out analyses.

Main Results:

• SS showed a genetic predisposition to increased risk of coronary (OR=1.046), cerebral (OR=1.320), and peripheral AS (OR=1.154).
• Reverse MR analysis indicated peripheral AS causally increases SS risk (OR=1.751).
• No significant reverse causal effects were found for coronary or cerebral AS on SS.

Conclusions:

• Presents genetic evidence for a bidirectional causal link between SS and peripheral AS.
• Suggests a unidirectional causal effect from SS to coronary and cerebral AS.
• Highlights the need for cardiovascular screening and integrated management for SS patients due to immune-vascular comorbidities.