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Variants in BET1L and TNRC6B associate with increasing fibroid volume and fibroid type among European Americans

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Abstract

Uterine fibroids (UFs) affect 77 % of women by menopause and account for $9.4 billion in yearly healthcare costs. We recently replicated findings from the first UF genome-wide association study (GWAS), conducted in the Japanese. Here we tested these GWAS-discovered SNPs for association with UF characteristics to further assess whether risk varies by sub-phenotypes of UFs. Women were enrolled in Right from the Start (RFTS) and the BioVU DNA repository (BioVU). UF status was determined by pelvic imaging. We tested the top GWAS-associated SNPs for association with UF characteristics (RFTS: type, number, volume; BioVU: type) using covariate adjusted logistic and linear regression. We also combined association results of UF type using meta-analysis. 456 European American (EA) cases and 1,549 controls were examined. Trinucleotide repeat containing 6B (TNRC6B) rs12484776 associated with volume in RFTS (β = 0.40, 95 % CI 0.05–0.75, p = 0.024). RFTS analyses evaluating stratified quartiles of volume showed the strongest OR at rs12484776 for the largest volume (16.6–179.1 cc, odds ratio (OR) = 2.19, 95 % confidence interval (CI) 1.07–4.46, p = 0.031). Meta-analysis showed a strong association at blocked early in transport 1 homolog (BET1L) rs2280543 for intramural UFs (meta-OR = 0.51, standard error (SE) = 0.14, Q = 0.590, I = 0, p = 2.48 × 10−6), which is stronger than the overall association with UF risk. This study is the first to evaluate these SNPs for association with UF characteristics and suggests these genes associate with increasing UF volume and protection from intramural UF in EAs.

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Acknowledgments

The field research for Right from the Start was supported by grants from the National Institute of Child and Human Development (R01HD043883 and R01HD049675) and the American Water Works Association Research Foundation (2579). Additional funds were provided by the Building Interdisciplinary Research Careers in Women’s Health career development program (2K12HD043483-11) to DRVE, the Vanderbilt Clinical and Translational Research Scholar Award 5KL2RR024977 to TLE from the National Center for Advancing Translational Sciences, the Vanderbilt CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences, and the BioVU dataset used for the analyses described was obtained from Vanderbilt University Medical Center’s BioVU which is supported by institutional funding and by the Vanderbilt CTSA Grant ULTR000445 from NCATS/NIH. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. No co-authors have any conflicts of interest to disclose and the material submitted for publication has not been previously reported and is not under consideration for publication elsewhere.

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Authors and Affiliations

  1. Vanderbilt Epidemiology Center, Vanderbilt University, 2525 West End Ave., Suite 600 6th Floor, Nashville, TN, 37203, USA

    Todd L. Edwards, Katherine E. Hartmann & Digna R. Velez Edwards

  2. Institute for Medicine and Public Health, Vanderbilt University, Nashville, USA

    Todd L. Edwards, Katherine E. Hartmann & Digna R. Velez Edwards

  3. Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA

    Todd L. Edwards & Digna R. Velez Edwards

  4. Division of Epidemiology, Department of Medicine, Vanderbilt University, Nashville, TN, USA

    Todd L. Edwards

  5. Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, USA

    Katherine E. Hartmann & Digna R. Velez Edwards

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  1. Todd L. Edwards
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Correspondence to Digna R. Velez Edwards.

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Edwards, T.L., Hartmann, K.E. & Velez Edwards, D.R. Variants in BET1L and TNRC6B associate with increasing fibroid volume and fibroid type among European Americans. Hum Genet 132, 1361–1369 (2013). https://doi.org/10.1007/s00439-013-1340-1

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