Causal Effects of Plasma Haptoglobin Levels on Alzheimer’s Disease: A Two-Sample Mendelian Randomization Study

Abstract

Background: A connection between plasma levels of haptoglobin (Hp) and Alzheimer’s disease (AD) has been shown in several observational studies. It is debatable, nonetheless, how the two are related causally. Objective: To establish the causal relationship between Hp and AD using a two-sample Mendelian randomization (MR) study. Methods: From the extensive genome-wide association studies and FinnGen dataset, summaries and statistics pertaining to AD were gathered. We investigated the possibility of a causal link between Hp and AD using a two-sample MR study. Inverse variance weighting was used as the primary analytical technique, and it was supported by the joint application of complementary analyses and fixed effects meta-analysis to combine results from various sources. Results: Genetically determined Hp was causally associated with AD [odds ratio (OR), 1.05; 95% confidence interval (CI), 1.02 to 1.09; p = 8.96×10–4]; Inverse variance-weighted estimates coming from different data sources were combined in a meta-analysis with consistent findings (OR, 1.03; 95% CI, 1.01 to 1.05; p = 2.00×10–3). The outcomes of the inverse MR analysis showed that AD had no appreciable causal impact on Hp. Conclusion: The present MR analysis shows that higher plasma Hp leads to an increased risk of AD. Strategies for plasma Hp testing may open up new doors for the early diagnosis and prevention of AD.