Dataset Information

Estimating Uterine Fibroid SNP-Based Heritability in European American Women with Imaging-Confirmed Fibroids.

ABSTRACT: BACKGROUND:Heritability 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. METHODS:Analyses 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. RESULTS:In 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. CONCLUSIONS:We 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.

SUBMITTER: Bray MJ

PROVIDER: S-EPMC6904850 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Estimating Uterine Fibroid SNP-Based Heritability in European American Women with Imaging-Confirmed Fibroids.

Bray Michael J MJ Davis Lea K LK Torstenson Eric S ES Jones Sarah H SH Edwards Todd L TL Velez Edwards Digna R DR

Human heredity 20190903 2

<h4>Background</h4>Heritability 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 herita ...[more]

PMID: 31480066

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Project description:OBJECTIVES:To examine the association between phthalate exposure and two measures of uterine fibroid burden: diameter of largest fibroid and uterine volume. DESIGN:Pilot, cross-sectional study. SETTING:Academic medical center. PATIENT(S):Fifty-seven premenopausal women undergoing either hysterectomy or myomectomy for fibroids. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):The diameter of the largest fibroid and uterine dimensions were abstracted from medical records. Spot urine samples were analyzed for 14 phthalate biomarkers using mass spectrometry. We estimated associations between fibroid outcomes and individual phthalate metabolites, sum of di(2-ethylhexyl) phthalate metabolites (?DEHP), and a weighted sum of anti-androgenic phthalate metabolites (?AA Phthalates) using linear regression, adjusting for age, race/ethnicity, and body mass index. Fibroid outcomes were also examined dichotomously (divided at the median) using logistic regression. RESULTS:Most women were of black ethnicity, overweight or obese, and college educated. In multivariable models, higher levels of mono-hydroxyisobutyl phthalate, monocarboxyoctyl phthalate, monocarboxynonyl phthalate, mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxyhexyl phthalate) (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), ?DEHP, and ?AA Phthalates were positively associated with uterine volume. Associations were most pronounced for individual DEHP metabolites (MEHHP, MEOHP, MECPP), ?DEHP, and ?AA Phthalates. For example, a doubling in ?DEHP and ?AA Phthalates was associated with 33.2% (95% confidence interval 6.6-66.5) and 26.8% (95% confidence interval 2.2-57.4) increase in uterine volume, respectively. There were few associations between phthalate biomarkers and fibroid size. CONCLUSIONS:Exposure to some phthalate biomarkers was positively associated with uterine volume, which further supports the hypothesis that phthalate exposures may be associated with fibroid outcomes. Additional studies are needed to confirm these relationships.

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.

Dataset Information

Estimating Uterine Fibroid SNP-Based Heritability in European American Women with Imaging-Confirmed Fibroids.

Publications

Estimating Uterine Fibroid SNP-Based Heritability in European American Women with Imaging-Confirmed Fibroids.

Similar Datasets

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