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...
Published in: | Nature Communications |
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2021
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Online Access: | https://pure.eur.nl/en/publications/59d19e82-87ab-4464-9f31-914985b7ce44 https://doi.org/10.1038/s41467-021-22338-2 https://pure.eur.nl/ws/files/50842090/Genetic_analysis_in_European_ancestry_individuals_identifies_517_loci_associated_with_liver_enzymes.pdf http://www.scopus.com/inward/record.url?scp=85105771079&partnerID=8YFLogxK |
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fturottercrispub:oai:pure.eur.nl:publications/59d19e82-87ab-4464-9f31-914985b7ce44 2023-05-15T17:42:32+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. Boezen, H. Marike Franke, Lude van der Harst, Pim Navis, Gerjan Rots, Marianne Swertz, Morris Wolffenbuttel, Bruce H.R. Wijmenga, Cisca 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 2021-05-10 application/pdf https://pure.eur.nl/en/publications/59d19e82-87ab-4464-9f31-914985b7ce44 https://doi.org/10.1038/s41467-021-22338-2 https://pure.eur.nl/ws/files/50842090/Genetic_analysis_in_European_ancestry_individuals_identifies_517_loci_associated_with_liver_enzymes.pdf http://www.scopus.com/inward/record.url?scp=85105771079&partnerID=8YFLogxK eng eng info:eu-repo/semantics/openAccess Pazoki , R , Vujkovic , M , Lifelines Cohort Study , the VA Million Veteran Program , Elliott , J , Evangelou , E , Gill , D , Ghanbari , M , van der Most , P J , Pinto , R C , Wielscher , M , Farlik , M , Zuber , V , de Knegt , R J , Snieder , H , Uitterlinden , A G , Boezen , H M , Franke , L , van der Harst , P , Navis , G , Rots , M , Swertz , M , Wolffenbuttel , B H R , Wijmenga , C , Lynch , J A , Jiang , X , Said , S , Kaplan , D E , Lee , K M , Serper , M , Carr , R M , Tsao , P S , Atkinson , S R , Dehghan , A , Tzoulaki , I , Ikram , M A , Herzig , K H , Järvelin , M R , Alizadeh , B Z , O’Donnell , C J , Saleheen , D , Voight , B F , Chang , K M , Thursz , M R & Elliott , P 2021 , ' Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes ' , Nature Communications , vol. 12 , no. 1 , 2579 . https://doi.org/10.1038/s41467-021-22338-2 /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being SDG 3 - Good Health and Well-being article 2021 fturottercrispub https://doi.org/10.1038/s41467-021-22338-2 2022-07-07T06:09:09Z 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 Erasmus University Rotterdam & Erasmus MC Research Portal Nature Communications 12 1 |
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Erasmus University Rotterdam & Erasmus MC Research Portal |
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fturottercrispub |
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English |
topic |
/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being SDG 3 - Good Health and Well-being |
spellingShingle |
/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being SDG 3 - Good Health and Well-being 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. Boezen, H. Marike Franke, Lude van der Harst, Pim Navis, Gerjan Rots, Marianne Swertz, Morris Wolffenbuttel, Bruce H.R. Wijmenga, Cisca 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 |
/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being SDG 3 - Good Health and Well-being |
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. Boezen, H. Marike Franke, Lude van der Harst, Pim Navis, Gerjan Rots, Marianne Swertz, Morris Wolffenbuttel, Bruce H.R. Wijmenga, Cisca 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. Boezen, H. Marike Franke, Lude van der Harst, Pim Navis, Gerjan Rots, Marianne Swertz, Morris Wolffenbuttel, Bruce H.R. Wijmenga, Cisca 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 |
publishDate |
2021 |
url |
https://pure.eur.nl/en/publications/59d19e82-87ab-4464-9f31-914985b7ce44 https://doi.org/10.1038/s41467-021-22338-2 https://pure.eur.nl/ws/files/50842090/Genetic_analysis_in_European_ancestry_individuals_identifies_517_loci_associated_with_liver_enzymes.pdf http://www.scopus.com/inward/record.url?scp=85105771079&partnerID=8YFLogxK |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_source |
Pazoki , R , Vujkovic , M , Lifelines Cohort Study , the VA Million Veteran Program , Elliott , J , Evangelou , E , Gill , D , Ghanbari , M , van der Most , P J , Pinto , R C , Wielscher , M , Farlik , M , Zuber , V , de Knegt , R J , Snieder , H , Uitterlinden , A G , Boezen , H M , Franke , L , van der Harst , P , Navis , G , Rots , M , Swertz , M , Wolffenbuttel , B H R , Wijmenga , C , Lynch , J A , Jiang , X , Said , S , Kaplan , D E , Lee , K M , Serper , M , Carr , R M , Tsao , P S , Atkinson , S R , Dehghan , A , Tzoulaki , I , Ikram , M A , Herzig , K H , Järvelin , M R , Alizadeh , B Z , O’Donnell , C J , Saleheen , D , Voight , B F , Chang , K M , Thursz , M R & Elliott , P 2021 , ' Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes ' , Nature Communications , vol. 12 , no. 1 , 2579 . https://doi.org/10.1038/s41467-021-22338-2 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1038/s41467-021-22338-2 |
container_title |
Nature Communications |
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12 |
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1 |
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1766144416138919936 |