Human genetics suggests differing causal pathways from HMGCR inhibition to coronary artery disease and type 2 diabetes.

ABSTRACT:

Background

Statins lower low-density lipoprotein cholesterol (LDL-C) and reduce the risk of coronary artery disease (CAD). However, they also increase the risk of type 2 diabetes (T2D).

Methods

We consider genetic variants in the region of the HMGCR gene, which encodes the target of statins, and their associations with downstream consequences of statins. We use various statistical methods to identify causal pathways influencing CAD and T2D, and investigate whether these are the same or different for the two diseases.

Results

Colocalization analyses indicate that LDL-C and body mass index (BMI) have distinct genetic predictors in this gene region, suggesting that they do not lie on the same causal pathway. Multivariable Mendelian randomization analyses restricted to va

SUBMITTER: Hwang S 

PROVIDER: S-EPMC12766909 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature