Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes
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. Rep...
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ftcdlib:oai:escholarship.org:ark:/13030/qt40j8569t 2023-09-05T13:21:56+02:00 Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes Pazoki, Raha Vujkovic, Marijana Elliott, Joshua Evangelou, Evangelos Gill, Dipender Ghanbari, Mohsen van der Most, Peter J Pinto, Rui Climaco Wielscher, Matthias Farlik, Matthias Zuber, Verena de Knegt, Robert J Snieder, Harold Uitterlinden, André G Lynch, Julie A Jiang, Xiyun Said, Saredo Kaplan, David E Lee, Kyung Min Serper, Marina Carr, Rotonya M Tsao, Philip S Atkinson, Stephen R Dehghan, Abbas Tzoulaki, Ioanna Ikram, M Arfan Herzig, Karl-Heinz Järvelin, Marjo-Riitta Alizadeh, Behrooz Z O’Donnell, Christopher J Saleheen, Danish Voight, Benjamin F Chang, Kyong-Mi Thursz, Mark R Elliott, Paul 2579 2021-05-01 application/pdf https://escholarship.org/uc/item/40j8569t unknown eScholarship, University of California qt40j8569t https://escholarship.org/uc/item/40j8569t public Nature Communications, vol 12, iss 1 Cardiovascular Digestive Diseases Heart Disease Liver Disease Genetics 2.1 Biological and endogenous factors Aetiology Oral and gastrointestinal Metabolic and endocrine Good Health and Well Being Aged Alanine Transaminase Alkaline Phosphatase Cardiovascular Diseases Cohort Studies Databases Genetic Female Gene Expression Regulation Enzymologic Genetic Predisposition to Disease Genetic Testing Genome-Wide Association Study Humans Insulin Resistance Lipid Metabolism Liver Male Mendelian Randomization Analysis Metabolic Diseases Middle Aged Polymorphism Single Nucleotide Risk Factors White People gamma-Glutamyltransferase Lifelines Cohort Study VA Million Veteran Program article 2021 ftcdlib 2023-08-21T18:07:21Z 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. Article in Journal/Newspaper Northern Finland University of California: eScholarship |
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University of California: eScholarship |
op_collection_id |
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language |
unknown |
topic |
Cardiovascular Digestive Diseases Heart Disease Liver Disease Genetics 2.1 Biological and endogenous factors Aetiology Oral and gastrointestinal Metabolic and endocrine Good Health and Well Being Aged Alanine Transaminase Alkaline Phosphatase Cardiovascular Diseases Cohort Studies Databases Genetic Female Gene Expression Regulation Enzymologic Genetic Predisposition to Disease Genetic Testing Genome-Wide Association Study Humans Insulin Resistance Lipid Metabolism Liver Male Mendelian Randomization Analysis Metabolic Diseases Middle Aged Polymorphism Single Nucleotide Risk Factors White People gamma-Glutamyltransferase Lifelines Cohort Study VA Million Veteran Program |
spellingShingle |
Cardiovascular Digestive Diseases Heart Disease Liver Disease Genetics 2.1 Biological and endogenous factors Aetiology Oral and gastrointestinal Metabolic and endocrine Good Health and Well Being Aged Alanine Transaminase Alkaline Phosphatase Cardiovascular Diseases Cohort Studies Databases Genetic Female Gene Expression Regulation Enzymologic Genetic Predisposition to Disease Genetic Testing Genome-Wide Association Study Humans Insulin Resistance Lipid Metabolism Liver Male Mendelian Randomization Analysis Metabolic Diseases Middle Aged Polymorphism Single Nucleotide Risk Factors White People gamma-Glutamyltransferase Lifelines Cohort Study VA Million Veteran Program Pazoki, Raha Vujkovic, Marijana Elliott, Joshua Evangelou, Evangelos Gill, Dipender Ghanbari, Mohsen van der Most, Peter J Pinto, Rui Climaco Wielscher, Matthias Farlik, Matthias Zuber, Verena de Knegt, Robert J Snieder, Harold Uitterlinden, André G Lynch, Julie A Jiang, Xiyun Said, Saredo Kaplan, David E Lee, Kyung Min Serper, Marina Carr, Rotonya M Tsao, Philip S Atkinson, Stephen R Dehghan, Abbas Tzoulaki, Ioanna Ikram, M Arfan Herzig, Karl-Heinz Järvelin, Marjo-Riitta Alizadeh, Behrooz Z O’Donnell, Christopher J Saleheen, Danish Voight, Benjamin F Chang, Kyong-Mi Thursz, Mark R Elliott, Paul Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes |
topic_facet |
Cardiovascular Digestive Diseases Heart Disease Liver Disease Genetics 2.1 Biological and endogenous factors Aetiology Oral and gastrointestinal Metabolic and endocrine Good Health and Well Being Aged Alanine Transaminase Alkaline Phosphatase Cardiovascular Diseases Cohort Studies Databases Genetic Female Gene Expression Regulation Enzymologic Genetic Predisposition to Disease Genetic Testing Genome-Wide Association Study Humans Insulin Resistance Lipid Metabolism Liver Male Mendelian Randomization Analysis Metabolic Diseases Middle Aged Polymorphism Single Nucleotide Risk Factors White People gamma-Glutamyltransferase Lifelines Cohort Study VA Million Veteran Program |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Pazoki, Raha Vujkovic, Marijana Elliott, Joshua Evangelou, Evangelos Gill, Dipender Ghanbari, Mohsen van der Most, Peter J Pinto, Rui Climaco Wielscher, Matthias Farlik, Matthias Zuber, Verena de Knegt, Robert J Snieder, Harold Uitterlinden, André G Lynch, Julie A Jiang, Xiyun Said, Saredo Kaplan, David E Lee, Kyung Min Serper, Marina Carr, Rotonya M Tsao, Philip S Atkinson, Stephen R Dehghan, Abbas Tzoulaki, Ioanna Ikram, M Arfan Herzig, Karl-Heinz Järvelin, Marjo-Riitta Alizadeh, Behrooz Z O’Donnell, Christopher J Saleheen, Danish Voight, Benjamin F Chang, Kyong-Mi Thursz, Mark R Elliott, Paul |
author_facet |
Pazoki, Raha Vujkovic, Marijana Elliott, Joshua Evangelou, Evangelos Gill, Dipender Ghanbari, Mohsen van der Most, Peter J Pinto, Rui Climaco Wielscher, Matthias Farlik, Matthias Zuber, Verena de Knegt, Robert J Snieder, Harold Uitterlinden, André G Lynch, Julie A Jiang, Xiyun Said, Saredo Kaplan, David E Lee, Kyung Min Serper, Marina Carr, Rotonya M Tsao, Philip S Atkinson, Stephen R Dehghan, Abbas Tzoulaki, Ioanna Ikram, M Arfan Herzig, Karl-Heinz Järvelin, Marjo-Riitta Alizadeh, Behrooz Z O’Donnell, Christopher J Saleheen, Danish Voight, Benjamin F Chang, Kyong-Mi Thursz, Mark R Elliott, Paul |
author_sort |
Pazoki, Raha |
title |
Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes |
title_short |
Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes |
title_full |
Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes |
title_fullStr |
Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes |
title_full_unstemmed |
Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes |
title_sort |
genetic analysis in european ancestry individuals identifies 517 loci associated with liver enzymes |
publisher |
eScholarship, University of California |
publishDate |
2021 |
url |
https://escholarship.org/uc/item/40j8569t |
op_coverage |
2579 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_source |
Nature Communications, vol 12, iss 1 |
op_relation |
qt40j8569t https://escholarship.org/uc/item/40j8569t |
op_rights |
public |
_version_ |
1776202488254300160 |