A mendelian randomization analysis of the associations between haptoglobin and multiple sclerosis

Observational studies have suggested an association between plasma haptoglobin and multiple sclerosis (MS). Haptoglobin plays an important role in the pathogenesis of MS. However, whether it has a causal effect on MS remains unknown.

We here used a two-sample bidirectional Mendelian randomization (MR) method to investigate the causality between haptoglobin and MS. Genetic variants associated with plasma haptoglobin from two independent genome wide association studies (GWASs) (used as the discovery and replication datasets, respectively) were applied as the exposure. Their causal effects on summary statistics of GWASs of MS and disease severity were evaluated using the inverse-variance weighted (IVW) approach as the main analysis component.

We found in both discovery and replication dataset that plasma haptoglobin was causally positively associated with the risk of MS (discovery: OR: 1.063, 95% CI: 1.022-1.106, P = 0.002; replication: OR: 1.041, 95% CI: 1.005-1.078, P = 0.026), but it was not associated with MS severity (discovery: OR: 1.017, 95% CI: 0.993-1.042, P = 0.168; replication: OR: 1.011, 95% CI: 0.987-1.036, P = 0.373). Besides, we did not detect any significant results in the reverse causation analysis.

Our study provides evidence for the causal effects of plasma haptoglobin on the risk of MS.