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Genome-wide meta-analysis identifies novel risk loci for uterine fibroids within and across multiple ancestry groups
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Genome-wide meta-analysis identifies novel risk loci for uterine fibroids within and across multiple ancestry groups
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Journal Article
Genome-wide meta-analysis identifies novel risk loci for uterine fibroids within and across multiple ancestry groups
2025
Overview
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.
Here, the authors present multi-ancestry genome-wide meta-analyses of uterine fibroids, identifying 11 new gene associations, and demonstrating that heritability is higher in African ancestries.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/43
/ Female
/ Fibroids
/ Genes
/ Genetic Predisposition to Disease
/ Genome-Wide Association Study
/ Genomes
/ Humanities and Social Sciences
/ Humans
/ Polymorphism, Single Nucleotide
/ Science
/ Single-nucleotide polymorphism
/ Uterine Neoplasms - ethnology
/ Uterine Neoplasms - genetics
/ Uterus
