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Tier 3 — Observational / field trialPeer-reviewed

A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation

Marijana Vujković, Shweta Ramdas, Kimberly Lorenz, Xiuqing Guo, Rebecca Darlay, Heather J. Cordell, Jing He, Yevgeniy Gindin, Chuhan Chung, Robert P. Myers, Carolin V. Schneider, Joseph Park, Kyung Min Lee, Marina Serper, Rotonya M. Carr, David E. Kaplan, Mary E. Haas, Matthew T. MacLean, Walter R. Witschey, Xiang Zhu, Catherine Tcheandjieu, Rachel L. Kember, Henry R. Kranzler, Anurag Verma, Ayush Giri, Derek Klarin, Yan V. Sun, Jie Huang, Jennifer E. Huffman, Kate Townsend Creasy, Nicholas J. Hand, Ching‐Ti Liu, Michelle T. Long, Jie Yao, Matthew J. Budoff, Jingyi Tan, Xiaohui Li, Henry J. Lin, Yii‐Der Ida Chen, Kent D. Taylor, Ruey‐Kang R. Chang, Ronald M. Krauss, Sílvia Vilarinho, Joseph Brancale, Jonas B. Nielsen, Adam E. Locke, Marcus B. Jones, Niek Verweij, Aris Baras, K. Rajender Reddy, Brent A. Neuschwander‐Tetri, Jeffrey B. Schwimmer, Arun J. Sanyal, Naga Chalasani, Kathleen A. Ryan, Braxton D. Mitchell, Dipender Gill, Andrew D. Wells, Elisabetta Manduchi, Yedidya Saiman, Nadim Mahmud, Donald R. Miller, Peter D. Reaven, Lawrence S. Phillips, Sumitra Muralidhar, Scott L. DuVall, Jennifer Lee, Themistocles L. Assimes, Saiju Pyarajan, Kelly Cho, Todd L. Edwards, Scott M. Damrauer, Peter W.F. Wilson, J. Michael Gaziano, Christopher J. O’Donnell, Amit V. Khera, Struan F.A. Grant, Christopher D. Brown, Philip S. Tsao, Danish Saleheen, Luca A. Lotta, Lisa Bastarache, Quentin M. Anstee, Ann K. Daly, James B. Meigs, Jerome I. Rotter, Julie A. Lynch, VA Million Veteran Program, Daniel J. Rader, Benjamin F. Voight, Kyong‐Mi Chang

Nature Genetics · 2022

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Summary

This multiancestry genome-wide association study identified genetic loci associated with unexplained chronic ALT elevation as a biomarker for nonalcoholic fatty liver disease, with findings validated against histological and radiological assessments. The work represents a large collaborative effort to map genetic susceptibility to NAFLD across diverse populations, as suggested by the involvement of the VA Million Veteran Program and multiple academic medical centres. The study contributes to understanding the heritable basis of NAFLD, a condition increasingly linked to metabolic and dietary factors.

UK applicability

The genetic findings may inform risk stratification and early detection of NAFLD in United Kingdom clinical populations, though ancestry-specific allele frequencies and effect sizes would require validation in UK cohorts. The study's identification of genetic drivers complements public health approaches to NAFLD prevention through diet and lifestyle modification in the NHS.

Key measures

Genetic variants (single nucleotide polymorphisms); ALT elevation; liver histology; radiological imaging; ancestry-stratified analyses

Outcomes reported

The study identified genetic variants associated with unexplained chronic ALT (alanine aminotransferase) elevation as a proxy for nonalcoholic fatty liver disease (NAFLD), validated against histological and radiological evidence. Findings were obtained across multiple ancestry groups to improve understanding of genetic risk factors for liver disease.

Theme
Nutrition & health
Subject
Dietary patterns & chronic disease
Study type
Research
Study design
Genome-wide association study (GWAS)
Source type
Peer-reviewed study
Status
Published
Geography
United States
System type
Human clinical
DOI
10.1038/s41588-022-01078-z
Catalogue ID
SNmojad27m-43ur1q

Topic tags

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