Genetic Analysis in European Ancestry Individuals Identifies 517 Loci Associated with Liver Enzymes

Overview

Journal Nat Commun

Specialty Biology

Date 2021 May 11

PMID 33972514

Citations 48

Authors

Raha Pazoki

Marijana Vujkovic

Joshua Elliott

Evangelos Evangelou

Dipender Gill

Mohsen Ghanbari

Peter J van der Most

Rui Climaco Pinto

Matthias Wielscher

Matthias Farlik

Verena Zuber

Robert J de Knegt

Harold Snieder

Andre G Uitterlinden

Julie A Lynch

Xiyun Jiang

Saredo Said

David E Kaplan

Kyung Min Lee

Marina Serper

Rotonya M Carr

Philip S Tsao

Stephen R Atkinson

Abbas Dehghan

Ioanna Tzoulaki

M Arfan Ikram

Karl-Heinz Herzig

Marjo-Riitta Jarvelin

Behrooz Z Alizadeh

Christopher J ODonnell

Danish Saleheen

Benjamin F Voight

Kyong-Mi Chang

Mark R Thursz

Paul Elliott

Affiliations

Soon will be listed here.

Abstract

Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.

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