Please use this identifier to cite or link to this item:
Title: Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes
Authors: Pazoki, R
Marijana, V
Joshua, E
Evangelos, E
Dipender, G
Mohsen, G
Peter, VDM
Rui, CP
Matthias, W
Matthias, F
Verena, Z
Robert, DK
Harold, S
André, U
Lifelines, S
Julie, L
Xiyun, J
Saredo, S
David, K
Kyung, ML
Marina, S
Rotonya, C
Phil, T
Stephen, A
Abbas, D
Ioanna, T
M. Arfan, I
Karl-Heinz, H
Marjo-Riitta, J
Behrooz Z., A
Christopher, O
Danish, S
Benjamin, V
Kyong-Mi, C
Mark, T
Paul, E
Issue Date: 10-May-2021
Publisher: Nature Research
Citation: Pazoki, R., Vujkovic, M., Elliott, J. et al. (2021) 'Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes', Nature Communications, 12, 2579, pp. 1-12. doi: 10.1038/s41467-021-22338-2.
Abstract: Copyright The Author(s). 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.
Other Identifiers: 2579
Appears in Collections:Dept of Life Sciences Research Papers

Files in This Item:
File Description SizeFormat 
FullText.pdf5.1 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons