Genome-wide meta-analysis identifies novel risk loci for uterine fibroids within and across multiple ancestry groups

Jeewoo Kim, Ariel Williams, Hannah Noh, Elizabeth A. Jasper, Sarah H. Jones, James A. Jaworski, Megan M. Shuey, Edward A. Ruiz-Narváez, Lauren A. Wise, Julie R. Palmer, John Connolly, Jacob M. Keaton, Joshua C. Denny, Atlas Khan, Mohammad A. Abbass, Laura J. Rasmussen-Torvik, Leah C. Kottyan, Purnima Madhivanan, Karl Krupp, Wei-Qi Wei, Todd L. Edwards, Digna R. Velez Edwards () and Jacklyn N. Hellwege ()
Additional contact information
Jeewoo Kim: Vanderbilt University Medical Center
Ariel Williams: National Institute of Health
Hannah Noh: Tufts University Medical School Graduate Programs
Elizabeth A. Jasper: Vanderbilt University Medical Center
Sarah H. Jones: Vanderbilt University Medical Center
James A. Jaworski: Vanderbilt University
Megan M. Shuey: Vanderbilt University Medical Center
Edward A. Ruiz-Narváez: Department of Nutritional Sciences University of Michigan School of Public Health
Lauren A. Wise: Boston University School of Public Health
Julie R. Palmer: Slone Epidemiology Center at Boston University
John Connolly: Children’s Hospital of Philadelphia
Jacob M. Keaton: National Institute of Health
Joshua C. Denny: National Institute of Health
Atlas Khan: Columbia University
Mohammad A. Abbass: Northwestern University Feinberg School of Medicine
Laura J. Rasmussen-Torvik: Northwestern University Feinberg School of Medicine
Leah C. Kottyan: University of Cincinnati
Purnima Madhivanan: University of Arizona Comprehensive Cancer Center
Karl Krupp: University of Arizona Comprehensive Cancer Center
Wei-Qi Wei: Vanderbilt University Medical Center
Todd L. Edwards: Vanderbilt University Medical Center
Digna R. Velez Edwards: Vanderbilt University Medical Center
Jacklyn N. Hellwege: Vanderbilt University Medical Center

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Uterine leiomyomata or fibroids are highly heritable, common, and benign tumors of the uterus with poorly understood etiology. Previous GWAS have reported 72 associated genes but included limited numbers of non-European individuals. Here, we identify 11 novel genes associated with fibroids across multi-ancestry and ancestry-stratified GWAS analyses. We replicate a known fibroid GWAS gene in African ancestry individuals and estimate the SNP-based heritability of fibroids in African ancestry populations as 15.9%. Using genetically predicted gene expression and colocalization analyses, we identify 46 novel genes associated with fibroids. These genes are significantly enriched in cancer, cell death and survival, reproductive system disease, and cellular growth and proliferation networks. We also find that increased predicted expression of HEATR3 in uterine tissue is associated with fibroids across ancestry strata. Overall, we report genetic variants associated with fibroids coupled with functional and gene pathway enrichment analyses.

Date: 2025
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DOI: 10.1038/s41467-025-57483-5

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