Trans-ancestry genome-wide association meta-analysis of gallstone disease
Abstract
Gallstone disease is a highly prevalent and costly gastrointestinal disease. Yet, genetic variation in gallstone susceptibility and its implication in metabolic pathways remain to be explored. We report a trans-ancestry genome-wide association meta-analysis of gallstone disease including 100,856 cases and 1,596,602 controls in the UK Biobank, FinnGen, Biobank Japan, and Million Veteran Program. We identified 116 (59 novel) risk loci across meta-analysis and found replication in statistically compelling signals in the All of Us Research Program. A polygenic risk score constructed from trans-ancestry lead variants was positively associated with liver chemistry and alpha-1-antitrypsin deficiency and negatively associated with total cholesterol and low-density lipoprotein levels among trans-ancestry and European ancestry groups in the Penn Medicine BioBank. Colocalization of risk loci with 44 traits and with expression quantitative trait loci from eight tissues yielded 321 and 110 significant colocalizations, respectively. These findings broaden our understanding of the genetic architecture of gallstone disease.
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BibTeX
@article{lim2026transancestry,
title = {{Trans-ancestry genome-wide association meta-analysis of gallstone disease}},
author = {Junghyun Lim and Marijana Vujkovic and Michael G. Levin and Kim Lorenz and Benjamin F. Voight and David Y. Zhang and Max. F. Dudek and Matthew C. Pahl and James A. Pippin and Chun Su and Elisabetta Manduchi and Andrew D. Wells and Struan F. A. Grant and Sarah Abramowitz and Scott M. Damrauer and Samiran Mukherjee and Guoyi Yang and Lindsay Guare and Shefali Setia-Verma and David E. Kaplan and Daniel J. Rader},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78644-0},
url = {https://www.nature.com/articles/s41467-026-78644-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Trans-ancestry genome-wide association meta-analysis of gallstone disease
AU - Junghyun Lim
AU - Marijana Vujkovic
AU - Michael G. Levin
AU - Kim Lorenz
AU - Benjamin F. Voight
AU - David Y. Zhang
AU - Max. F. Dudek
AU - Matthew C. Pahl
AU - James A. Pippin
AU - Chun Su
AU - Elisabetta Manduchi
AU - Andrew D. Wells
AU - Struan F. A. Grant
AU - Sarah Abramowitz
AU - Scott M. Damrauer
AU - Samiran Mukherjee
AU - Guoyi Yang
AU - Lindsay Guare
AU - Shefali Setia-Verma
AU - David E. Kaplan
AU - Daniel J. Rader
PY - 2026
DA - 2026/10/22
JO - Nature Communications
DO - 10.1038/s41467-026-78644-0
UR - https://www.nature.com/articles/s41467-026-78644-0
AB - Gallstone disease is a highly prevalent and costly gastrointestinal disease. Yet, genetic variation in gallstone susceptibility and its implication in metabolic pathways remain to be explored. We report a trans-ancestry genome-wide association meta-analysis of gallstone disease including 100,856 cases and 1,596,602 controls in the UK Biobank, FinnGen, Biobank Japan, and Million Veteran Program. We identified 116 (59 novel) risk loci across meta-analysis and found replication in statistically compelling signals in the All of Us Research Program. A polygenic risk score constructed from trans-ancestry lead variants was positively associated with liver chemistry and alpha-1-antitrypsin deficiency and negatively associated with total cholesterol and low-density lipoprotein levels among trans-ancestry and European ancestry groups in the Penn Medicine BioBank. Colocalization of risk loci with 44 traits and with expression quantitative trait loci from eight tissues yielded 321 and 110 significant colocalizations, respectively. These findings broaden our understanding of the genetic architecture of gallstone disease.
SN - 2041-1723
ER -