@article{3362a807b88d46c983d8ddc2f5d77c24,
title = "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.",
author = "{Lifelines Cohort Study} and {the VA Million Veteran Program} and Raha Pazoki and Marijana Vujkovic and Joshua Elliott and Evangelos Evangelou and Dipender Gill and Mohsen Ghanbari and {van der Most}, {Peter J.} and Pinto, {Rui Climaco} and Matthias Wielscher and Matthias Farlik and Verena Zuber and {de Knegt}, {Robert J.} and Harold Snieder and Uitterlinden, {Andr{\'e} G.} and Boezen, {H. Marike} and Lude Franke and {van der Harst}, Pim and Gerjan Navis and Marianne Rots and Morris Swertz and Wolffenbuttel, {Bruce H.R.} and Cisca Wijmenga and Lynch, {Julie A.} and Xiyun Jiang and Saredo Said and Kaplan, {David E.} and Lee, {Kyung Min} and Marina Serper and Carr, {Rotonya M.} and Tsao, {Philip S.} and Atkinson, {Stephen R.} and Abbas Dehghan and Ioanna Tzoulaki and Ikram, {M. Arfan} and Herzig, {Karl Heinz} and J{\"a}rvelin, {Marjo Riitta} and Alizadeh, {Behrooz Z.} and O{\textquoteright}Donnell, {Christopher J.} and Danish Saleheen and Voight, {Benjamin F.} and Chang, {Kyong Mi} and Thursz, {Mark R.} and Paul Elliott and Ballas, {Zuhair K.} and Sujata Bhushan and Boyko, {Edward J.} and Cohen, {David M.} and John Concato and Michaela Aslan and Hongyu Zhao and Constans, {Joseph I.} and Dellitalia, {Louis J.} and Fayad, {Joseph M.} and Fernando, {Ronald S.} and Florez, {Hermes J.} and Gaddy, {Melinda A.} and Gappy, {Saib S.} and Gretchen Gibson and Michael Godschalk and Greco, {Jennifer A.} and Samir Gupta and Salvador Gutierrez and Hammer, {Kimberly D.} and Hamner, {Mark B.} and Harley, {John B.} and Hung, {Adriana M.} and Mostaqul Huq and Hurley, {Robin A.} and Iruvanti, {Pran R.} and Ivins, {Douglas J.} and Jacono, {Frank J.} and Jhala, {Darshana N.} and Kaminsky, {Laurence S.} and Klein, {Jon B.} and Suthat Liangpunsakul and Lichy, {Jack H.} and Jennifer Moser and Huang, {Grant D.} and Sumitra Muralidhar and Mastorides, {Stephen M.} and Mathew, {Roy O.} and Mattocks, {Kristin M.} and Rachel McArdle and Meyer, {Paul N.} and Meyer, {Laurence J.} and Moorman, {Jonathan P.} and Morgan, {Timothy R.} and Maureen Murdoch and Okusaga, {Olaoluwa O.} and Oursler, {Kris Ann K.} and Ratcliffe, {Nora R.} and Rauchman, {Michael I.} and Robey, {R. Brooks} and Ross, {George W.} and Servatius, {Richard J.} and Sharma, {Satish C.} and Sherman, {Scott E.} and Elif Sonel and Peruvemba Sriram and Todd Stapley and Striker, {Robert T.} and Neeraj Tandon and Gerardo Villareal and Wallbom, {Agnes S.} and Wells, {John M.} and Whittle, {Jeffrey C.} and Whooley, {Mary A.} and Wilson, {Peter W.} and Sun, {Yan V.} and Junzhe Xu and Yeh, {Shing Shing} and Todd Connor and Argyres, {Dean P.} and Hauser, {Elizabeth R.} and Beckham, {Jean C.} and Brady Stephens and Aguayo, {Samuel M.} and Ahuja, {Sunil K.} and Saiju Pyarajan and Kelly Cho and Gaziano, {J. Michael} and Scott Kinlay and Nguyen, {Xuan Mai T.} and Brewer, {Jessica V.} and Brophy, {Mary T.} and Do, {Nhan V.} and Humphries, {Donald E.} and Selva, {Luis E.} and Shahpoor Shayan and Whitbourne, {Stacey B.} and Breeling, {Jim L.} and Romero, {J. P.Casas} and Ramoni, {Rachel B.}",
note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41467-021-22338-2",
language = "English",
volume = "12",
journal = "Nature communications",
issn = "2041-1723",
number = "1",
}