Multi-cohort genome-wide association analyses reveal loci underlying circulating liver enzyme levels in African-ancestry populations

Multi-cohort genome-wide association analyses reveal loci underlying circulating liver enzyme levels in African-ancestry populations | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Multi-cohort genome-wide association analyses reveal loci underlying circulating liver enzyme levels in African-ancestry populations Adebowale Adeyemo, Reagan Mogire, Guanjie Chen, Ayo Doumatey, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6941679/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Liver enzymes are critical biomarkers of hepatic metabolism, injury, and systemic homeostasis. Their genetic architecture remains understudied in African-ancestry populations. We addressed this knowledge gap by conducting genome-wide analyses of four liver enzymes in over 55,000 individuals of African ancestry from six cohorts across sub-Saharan Africa, the United States, and the United Kingdom. We identified 31 significant loci, of which 14 were novel, including TMEM64 and CRYL1 for alkaline phosphatase, IMMP2L for alanine aminotransferase, and PDE4D for gamma-glutamyl transferase. Several novel variants exhibited high allele frequencies in African-ancestry populations but were rare or absent in other global populations. Functional annotation indicated that lead variants overlapped liver-active regulatory regions, histone marks, and hepatocyte eQTLs. Colocalization and enrichment analyses implicated pathways related to lipid and carbohydrate metabolism, glycosylation, and immune function. Our findings expand the catalog of genetic variants influencing liver enzymes and advance understanding of the biological mechanisms underlying liver function. Biological sciences/Biotechnology/Genomics Biological sciences/Genetics/Genetic association study/Genome-wide association studies Biological sciences/Genetics/Population genetics Genome-wide association study liver enzymes liver function African ancestry alanine aminotransferase Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryDatasets.xlsx Additional Supplementary Data Files Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6941679","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":476802866,"identity":"ecd620fc-212e-476b-a22b-c8f4bfc3709f","order_by":0,"name":"Adebowale 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