Bidirectional Association between Atrial Fibrillation and Ovarian Cancer: Evidence from the UK Biobank and Mendelian...

Area of Science:

• Cardiology
• Oncology
• Genetics

Background:

• Atrial fibrillation (AF) and ovarian cancer are significant health concerns with potential links.
• The temporal and genetic relationship between AF and ovarian cancer requires clarification.

Purpose of the Study:

• To investigate the bidirectional association between atrial fibrillation and ovarian cancer.
• To explore the genetic underpinnings of the relationship between AF and ovarian cancer using Mendelian randomization.

Main Methods:

• Utilized UK Biobank data from 265,248 women for bidirectional Cox models.
• Employed two-sample Mendelian randomization (MR) to assess genetically proxied AF liability on ovarian cancer risk.
• Conducted summary data-based MR and functional genomic analyses to identify shared genes and evaluate biological plausibility.

Main Results:

• Observational data showed AF increased ovarian cancer risk (HR, 1.30) and vice versa (HR, 1.75).
• MR analyses indicated a modest genetic association of AF liability with ovarian cancer risk (OR, 1.05).
• Identified nucleoporin 50 and synaptotagmin-like 2 as shared susceptibility genes, with knockdown inhibiting ovarian cancer cell proliferation.

Conclusions:

• The study provides observational and genetic evidence linking AF and ovarian cancer.
• MR analyses support a genetic contribution of AF liability to ovarian cancer risk.
• Nucleoporin 50 and synaptotagmin-like 2 are nominated as potential mediators in the AF-ovarian cancer connection.