Genome-wide association study of serum liver enzymes implicates diverse metabolic and liver pathology
Vincent Chen, Xiaomeng Du, Yanhua Chen, Annapurna Kuppa, Samuel K. Handelman, Rishel B. Vohnoutka, Patricia A. Peyser, Nicholette D. Palmer, Lawrence F. Bielak, Brian Halligan, Elizabeth K. Speliotes
Abstract
Serum liver enzyme concentrations are the most frequently-used laboratory markers of liver disease, a major cause of mortality. We conduct a meta-analysis of genome-wide association studies of liver enzymes from UK BioBank and BioBank Japan. We identified 160 previously-unreported independent alanine aminotransferase, 190 aspartate aminotransferase, and 199 alkaline phosphatase genome-wide significant associations, with some affecting multiple different enzymes. Associated variants implicate genes that demonstrate diverse liver cell type expression and promote a range of metabolic and liver diseases. These findings provide insight into the pathophysiology of liver and other metabolic diseases that are associated with serum liver enzyme concentrations.