Figure 1.

Locus zoom plot of the lead variant (rs116843064) in ANGPTL4 from the PheGWAS available at University of Michigan’s PheWeb. The variant is associated with coronary atherosclerosis (P-value <1.6e−7) in 20 023 cases and 377 103 controls in UKBB. The variant is also associated with other phenotypes at phenome-wide significance (P-value < 5e−5) including hypercholesterolemia and ischemic heart disease as expected. Notably, this variant is also associated with ankylosing spondylitis—a form of arthritis affecting the spine and large joints. While ankylosing spondylitis is seemingly pathologically different than CAD, a link between the two has been reported previously (51). The constellation of associations across circulatory, metabolic and musculoskeletal systems provides evidence for pleiotropy or shared pathways for disease pathogenesis.