Pazoki, R;
Vujkovic, M;
Elliott, J;
Evangelou, E;
Gill, D;
Ghanbari, M;
van der Most, PJ;
Pinto, RC;
Wielscher, M;
Farlik, M;
et al.
Pazoki, R; Vujkovic, M; Elliott, J; Evangelou, E; Gill, D; Ghanbari, M; van der Most, PJ; Pinto, RC; Wielscher, M; Farlik, M; Zuber, V; de Knegt, RJ; Snieder, H; Uitterlinden, AG; Lifelines Cohort Study; Lynch, JA; Jiang, X; Said, S; Kaplan, DE; Lee, KM; Serper, M; Carr, RM; Tsao, PS; Atkinson, SR; Dehghan, A; Tzoulaki, I; Ikram, MA; Herzig, K-H; Järvelin, M-R; Alizadeh, BZ; O'Donnell, CJ; Saleheen, D; Voight, BF; Chang, K-M; Thursz, MR; Elliott, P; VA Million Veteran Program
(2021)
Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.
Nat Commun, 12 (1).
p. 2579.
ISSN 2041-1723
https://doi.org/10.1038/s41467-021-22338-2
SGUL Authors: Gill, Dipender Preet Singh
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.
| Item Type: |
Article
|
| Additional Information: |
Open Access This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2021 |
| Keywords: |
Lifelines Cohort Study, VA Million Veteran Program, MD Multidisciplinary |
| SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
| Journal or Publication Title: |
Nat Commun |
| ISSN: |
2041-1723 |
| Language: |
eng |
| Dates: |
| Date | Event |
|---|
| 10 May 2021 | Published | | 5 February 2021 | Accepted |
|
| Publisher License: |
Creative Commons: Attribution 4.0 |
| Projects: |
|
| PubMed ID: |
33972514 |
 |
Go to PubMed abstract |
| URI: |
https://openaccess.sgul.ac.uk/id/eprint/113269 |
| Publisher's version: |
https://doi.org/10.1038/s41467-021-22338-2 |
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