Genome-wide association study of serum liver enzymes implicates diverse metabolic and liver pathology

Vincent L. Chen, Xiaomeng Du, Yanhua Chen, Annapurna Kuppa, Samuel K. Handelman, Rishel B. Vohnoutka, Patricia A. Peyser, Nicholette D. Palmer, Lawrence F. Bielak, Brian Halligan and Elizabeth K. Speliotes ()
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Vincent L. Chen: University of Michigan Health System
Xiaomeng Du: University of Michigan Health System
Yanhua Chen: University of Michigan Health System
Annapurna Kuppa: University of Michigan Health System
Samuel K. Handelman: University of Michigan Health System
Rishel B. Vohnoutka: University of Michigan Health System
Patricia A. Peyser: University of Michigan School of Public Health
Nicholette D. Palmer: Wake Forest School of Medicine
Lawrence F. Bielak: University of Michigan School of Public Health
Brian Halligan: University of Michigan Health System
Elizabeth K. Speliotes: University of Michigan Health System

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20870-1

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