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Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.

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.

SUBMITTER: Pazoki R

PROVIDER: S-EPMC8110798 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.

Pazoki Raha R Vujkovic Marijana M Elliott Joshua J Evangelou Evangelos E Gill Dipender D Ghanbari Mohsen M van der Most Peter J PJ Pinto Rui Climaco RC Wielscher Matthias M Farlik Matthias M Zuber Verena V de Knegt Robert J RJ Snieder Harold H Uitterlinden André G AG Lynch Julie A JA Jiang Xiyun X Said Saredo S Kaplan David E DE Lee Kyung Min KM Serper Marina M Carr Rotonya M RM Tsao Philip S PS Atkinson Stephen R SR Dehghan Abbas A Tzoulaki Ioanna I Ikram M Arfan MA Herzig Karl-Heinz KH Järvelin Marjo-Riitta MR Alizadeh Behrooz Z BZ O'Donnell Christopher J CJ Saleheen Danish D Voight Benjamin F BF Chang Kyong-Mi KM Thursz Mark R MR Elliott Paul P

Nature communications 20210510 1

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 identif ...[more]

PMID: 33972514

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Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.

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Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.

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