Dataset Information

Admixture mapping of uterine fibroid size and number in African American women.

ABSTRACT: OBJECTIVE:To evaluate the relationship between genetic ancestry and uterine fibroid characteristics. DESIGN:Cross-sectional study. SETTING:Not applicable. PATIENT(S):A total of 609 African American participants with image- or surgery-confirmed fibroids in a biorepository at Vanderbilt University electronic health record biorepository and the Coronary Artery Risk Development in Young Adults studies were included. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):Outcome measures include fibroid number (single vs. multiple), volume of largest fibroid, and largest fibroid dimension of all fibroid measurements. RESULT(S):Global ancestry meta-analyses revealed a significant inverse association between percentage of European ancestry and risk of multiple fibroids (odds ratio: 0.78; 95% confidence interval 0.66, 0.93; P=6.05 × 10-3). Local ancestry meta-analyses revealed five suggestive (P<4.80 × 10-3) admixture mapping peaks in 2q14.3-2q21.1, 3p14.2-3p14.1, 7q32.2-7q33, 10q21.1, 14q24.2-14q24.3, for number of fibroids and one suggestive admixture mapping peak (P<1.97 × 10-3) in 10q24.1-10q24.32 for volume of largest fibroid. Single variant association meta-analyses of the strongest associated region from admixture mapping of fibroid number (10q21.1) revealed a strong association at single nucleotide polymorphism variant rs12219990 (odds ratio: 0.41; 95% confidence interval 0.28, 0.60; P=3.82 × 10-6) that was significant after correction for multiple testing. CONCLUSION(S):Increasing African ancestry is associated with multiple fibroids but not with fibroid size. Local ancestry analyses identified several novel genomic regions not previously associated with fibroid number and increasing volume. Future studies are needed to explore the genetic impact that ancestry plays into the development of fibroid characteristics.

SUBMITTER: Bray MJ

PROVIDER: S-EPMC5728674 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Admixture mapping of uterine fibroid size and number in African American women.

Bray Michael J MJ Edwards Todd L TL Wellons Melissa F MF Jones Sarah H SH Hartmann Katherine E KE Velez Edwards Digna R DR

Fertility and sterility 20171201 6

<h4>Objective</h4>To evaluate the relationship between genetic ancestry and uterine fibroid characteristics.<h4>Design</h4>Cross-sectional study.<h4>Setting</h4>Not applicable.<h4>Patient(s)</h4>A total of 609 African American participants with image- or surgery-confirmed fibroids in a biorepository at Vanderbilt University electronic health record biorepository and the Coronary Artery Risk Development in Young Adults studies were included.<h4>Intervention(s)</h4>None.<h4>Main outcome measure(s) ...[more]

PMID: 29202956

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Project description:ImportanceUterine fibroids are an understudied condition, with earlier onset in Black than White women. Prior studies of the importance of family history on fibroid development are limited by reliance on hospital-based participant selection, poorly defined measures of family history, and nonsystematic fibroid assessment.ObjectiveTo examine whether family history is a risk factor for fibroid development using prospective ultrasonography data to identify incident fibroids and measure fibroid growth and standardized methods to ascertain family history.Design, setting, and participantsThis prospective community cohort of Black and African American women from the Detroit, Michigan, area was conducted from January 1, 2010, to December 31, 2018, using 4 standardized ultrasonographic examinations during 5 years to detect fibroids 0.5 cm or larger in diameter and measure fibroid growth. Data analysis was performed between May 2022 and January 2024.ExposuresMaternal fibroid history data were gathered directly from participants' mothers when possible (1425/1628 [88%]), and 2 exposure variables were created: maternal history of fibroids (diagnosed vs not diagnosed) and age at maternal fibroid diagnosis (20-29, 30-39, or ≥40 years vs not diagnosed).Main outcomes and measuresFibroid incidence was assessed using multivariable Cox proportional hazards regression models; fibroid growth was calculated as change in log-volume per 18 months for fibroids matched at successive ultrasonograms.ResultsA total of 1610 self-identified Black and/or African American women aged 23 to 35 years (mean [SD] age, 29.2 [3.4] years) with no prior clinical diagnosis of fibroids at enrollment were available for analysis. Of 1187 fibroid-free participants at enrollment, 442 (37%) had mothers who were diagnosed with fibroids. Compared with participants without a maternal history of fibroids, those reporting maternal history had an adjusted hazard ratio (AHR) of 1.21 (95% CI, 0.96-1.52). Risk was strongest in those whose mothers were diagnosed at a younger age (20-29 years: AHR, 1.56; 95% CI, 1.11-2.21; 30-39 years: AHR, 1.03; 95% CI, 0.71-1.49; ≥40 years: AHR, 1.11; 95% CI, 0.81-1.52; P = .053 for trend). Fibroid growth rates were higher when mothers were diagnosed with fibroids vs not diagnosed (8.0% increased growth; 95% CI, -1.2% to 18.0%).Conclusions and relevanceIn this prospective cohort study, results supported maternal history of fibroids as a risk factor for incident fibroids, especially when mothers were diagnosed at a younger age. Maternal history was also associated with increased fibroid growth. Asking patients about their family history of fibroids could encourage patient self-advocacy and inform care.

Project description:BackgroundUterine fibroids are highly prevalent, benign tumors. They are the leading indication for hysterectomy, and Black women are disproportionally burdened. Soy-based infant formula contains phytoestrogens, and exposure during sensitive developmental windows may adversely affect the developing uterus; early phytoestrogen treatment in rodent studies led to detrimental uterine effects, including increased fibroid risk in Eker rats. Limited epidemiological studies also have suggested increased fibroid development with soy formula infant feeding.ObjectiveThe goal of this study was to examine the association between soy formula feeding in infancy and fibroid development in adulthood.MethodsWe evaluated this association among 1,610 Black/African-American women age 23-35 y in the Study of Environment, Lifestyle & Fibroids (SELF). Soy formula feeding data was gathered directly from the participants' mothers (89%). A standardized ultrasound examination was conducted during 4 clinic visits over 5 y to detect fibroids ≥0.5cm in diameter. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between soy formula feeding and incident fibroids adjusted for early-life and adult factors. Fibroid growth was calculated as change in log-volume for fibroids matched at successive visits.ResultsOf 1,121 fibroid-free participants at baseline, 150 (13%) were ever fed soy formula as infants, and 269 (24%) developed incident fibroids. We did not observe an association between ever being fed soy formula and incident fibroid risk (HR=1.08; 95% CI: 0.75, 1.54). However, participants fed soy formula within 2 months of birth and for >6 months (n=53) had an elevated risk of fibroid incidence in comparison with those never fed soy formula (HR=1.56; 95% CI: 0.92, 2.65). Fibroid growth rates did not differ.DiscussionAdding support to limited human data, this prospective fibroid study found that soy-based formula feeding during infancy was associated with a suggestive increase in risk of ultrasound-identified incident fibroids in adulthood. https://doi.org/10.1289/EHP11089.

Project description:BackgroundHeritability estimates (including twin and single nucleotide polymorphism [SNP]-based heritability studies) for fibroids have been inconsistent across prior studies ranging between 9 and 69%. These inconsistencies are due to variations in study design and included populations. A major design issue has been lack of imaging confirmation to identify controls, where asymptomatic women without imaging confirmation may be misclassified as controls leading to an attenuation of heritability estimates. To reconcile the differences in prior heritability estimates and the impact of misclassification of controls on heritability, we determined SNP-based heritability and characterized the genetic architecture of pelvic image-confirmed fibroid cases and controls.MethodsAnalyses were performed among women of European American descent using genome-wide SNP data from BioVU, a clinical database composed of DNA linked to de-identified electronic health records. We estimated the genetic variance explained by all SNPs using Genome-Wide Complex Trait Analysis on imputed data. Fibroid cases and controls were identified using a previously reported phenotyping algorithm that required pelvic imaging confirmation.ResultsIn total, we used 1,067 image-confirmed fibroid cases and 1,042 image-confirmed fibroid controls. The SNP-based heritability estimate for fibroid risk was h2 = 0.33 ± 0.18 (p = 0.040). We investigated the relationship between heritability per chromosome and chromosome length (r2 < 1%), with chromosome 8 explaining the highest proportion of variance for fibroid risk. There was no enrichment for intergenic or genic SNPs for the fibroid SNP-based heritability. Excluding loci previously associated with fibroid risk from genome-wide association study did not attenuate fibroid heritability suggesting that loci associating with fibroid risk are yet to be discovered.ConclusionsWe observed that fibroid SNP-based heritability was higher than the previous estimate using genome-wide SNP data that relied on self-reported outcomes, but within the range of prior twin pair studies. Furthermore, these data support that imprecise phenotyping can significantly affect the ability to estimate heritability using genotype data.

Dataset Information

Admixture mapping of uterine fibroid size and number in African American women.

Publications

Admixture mapping of uterine fibroid size and number in African American women.

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