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Identify novel and ancestry-specific genetic risk loci associated with uterine fibroids across women of European and African ancestry using a two-stage genome-wide approach.

June 12, 2019Frontiers in GeneticsOpen Access

A Trans-Ethnic Genome-Wide Association Study of Uterine Fibroids

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Identify novel and ancestry-specific genetic risk loci associated with uterine fibroids across women of European and African ancestry using a two-stage genome-wide approach.
Conducted a two-stage case-control meta-analysis across seven eMERGE sites (3,704 imaging-confirmed cases, 5,591 controls) and UK Biobank (discovery: 5,772 cases, 61,457 controls; replication: 12,358 cases, 138,477 controls).
Evaluated genetic variants imputed to a 1000 Genomes reference using race- and site-adjusted logistic regression models followed by fixed-effects meta-analysis (total N=21,804 cases and 205,525 controls).
Assessed genetically predicted tissue-specific gene expression and performed single-nucleotide polymorphism-based summary Mendelian randomization analysis.
Identified 326 genome-wide significant variants across 11 loci, including three novel loci at chromosome 1q24 (rs14361789; P=4.7x10-8), chromosome 16q12.1 (rs4785384; P=1.5x10-9), and chromosome 20q13.1 (rs6094982; P=2.6x10-8).
Demonstrated ancestry-specific effects for sentinel SNP rs10917151 in the CDC42/WNT4 locus (P=1.76x10-24; P-Het=0.04), showing protective association in African ancestry (OR=0.84) and increased risk in European ancestry (OR=1.16).
Identified associations between fibroids and genetically predicted gene expression of LUZP1 (P=4.6x10-8), OBFC1 (P=8.7x10-8), NUDT13 (P=3.3x10-6), and HEATR3 (P=5.8x10-6, supported by summary Mendelian randomization).

Authors

TETodd L. EdwardsVanderbilt University Medical Center AGAyush GiriNational Academy of Medicine JHJacklyn N. HellwegeVanderbilt University Medical Center

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Implication

Genome-wide association meta-analysis reveals novel and ancestry-specific risk loci for uterine fibroids in diverse populations, highlighting regulatory mechanisms in disease pathogenesis.

Cite This Study

Edwards et al. (2019) studied this question.

synapsesocial.com/papers/6a75fd4832e180ccc08b7605 https://doi.org/10.3389/fgene.2019.00511

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Implication

Genome-wide association meta-analysis reveals novel and ancestry-specific risk loci for uterine fibroids in diverse populations, highlighting regulatory mechanisms in disease pathogenesis.

A Trans-Ethnic Genome-Wide Association Study of Uterine Fibroids

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Discussion

Implication

Cite This Study

A Trans-Ethnic Genome-Wide Association Study of Uterine Fibroids

Key Points

Discussion

Implication

Cite This Study