Sex hormones and 14 autoimmune diseases: The causal relationship from a bidirectional 2-sample Mendelian...

Area of Science:

• Endocrinology and Immunology
• Genetics and Epidemiology

Background:

• Observational studies suggest links between sex hormones and autoimmune diseases (ADs).
• Causality of these associations remains uncertain.
• Investigating genetic predispositions offers insights into disease mechanisms.

Purpose of the Study:

• To investigate the causal relationship between sex hormones and the risk of 14 common autoimmune diseases (ADs).
• To explore bidirectional causal associations between sex hormones and ADs using Mendelian randomization.

Main Methods:

• Bidirectional Mendelian randomization (MR) analysis using genome-wide association study summary statistics.
• Evaluated associations between five sex hormones/binding globulin and 14 ADs.
• Employed inverse variance weighted, MR Egger, weighted median, and Wald ratio methods with sensitivity analyses.

Main Results:

• Higher total testosterone linked to decreased risk of ankylosing spondylitis, type 1 diabetes, and primary biliary cholangitis.
• Higher estradiol associated with increased celiac disease risk; dehydroepiandrosterone sulfate linked to increased vitiligo risk.
• Sex-hormone-binding globulin associated with increased rheumatoid arthritis and multiple sclerosis risk, but decreased type 1 diabetes risk.

Conclusions:

• Demonstrates causal associations between specific sex hormones and the risk of various autoimmune diseases.
• Findings provide insights into AD pathogenesis and suggest potential therapeutic strategies involving hormone modulation.
• Highlights the potential of targeting sex hormone levels for AD prevention and treatment.