Genetically predicted mannose-binding lectin levels and risk of future venous thromboembolism—the HUNT Study

BACKGROUND: Elevated plasma mannose-binding lectin (MBL) levels are associated with increased risk of venous thromboembolism (VTE). Although MBL levels are affected by environmental factors, it is mainly genetically regulated. OBJECTIVES: We aimed to investigate the association between genetically predicted MBL and VTE risk in a population-based cohort. METHODS: The study comprised 68 999 individuals from the Trøndelag Health Study (HUNT). Six genetic variants were used to classify individuals in low, medium, and high genetically predicted MBL. Linear regression was applied to estimate whether genetically predicted MBL explained plasma variability of MBL. Cox regression was used to estimate hazard ratios (HRs) with 95% CIs for VTE across genetically predicted MBL categories stratified by sex (men and women) and age groups (reference: low category). RESULTS: There were 2043 incident VTEs during 12 years' median follow-up. Genetically predicted MBL explained 52.8% of the plasma variability of MBL, and women had lower plasma MBL than men. Genetically predicted MBL was associated with a significantly increased risk of VTE in individuals