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Objective: To identify, through genome-wide association studies, genetic loci that associate with differences in fibroid size and number in a population of African American and European American women., Design: Cross-sectional study., Setting: Not applicable., Patient(s): Using BioVU, a clinical population from the Vanderbilt University Medical Center, and the Coronary Artery Risk Development in Young Adults cohort, a prospective cohort, we identified 1520 women (609 African American and 911 European American) with documented fibroid characteristics., Intervention(s): None., Main Outcome Measure(s): Outcome measurements include volume of largest fibroid, largest fibroid dimension, and number of fibroids (single vs. multiple)., Result(s): In race-stratified analyses we achieved genome-wide significance at a variant located between MAT2B and TENM2 (rs57542984, β = 0.13; 95% confidence interval 0.09, 0.17) for analyses of largest fibroid dimension in African Americans. The strongest signal for transethnic analyses was at a variant on 1q31.1 located between PLA2G4A and BRINP3 (rs6605005, β = 0.24; 95% confidence interval 0.15, 0.33) for fibroid volume. Results from MetaXcan identified an association between predicted expression of the gene ER degradation enhancing alpha-mannosidase like protein 2 (EDEM2) in the thyroid and number of fibroids (Z score = -4.51)., Conclusion(s): This study identified many novel associations between genetic loci and fibroid size and number in both race-stratified and transethnic analyses. Future studies are necessary to further validate our study findings and to better understand the mechanisms underlying these associations., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: We previously demonstrated an association between European mitochondrial haplogroups and proliferative diabetic retinopathy (PDR). The purpose of this study was to determine how the relationship between these haplogroups and both diabetes duration and hyperglycemia, two major risk factors for diabetic retinopathy (DR), affect PDR prevalence., Methods: Our population consisted of patients with type 2 diabetes with (n = 377) and without (n = 480) DR. A Kruskal-Wallis test was used to compare diabetes duration and hemoglobin A1c (HbA1c) among mitochondrial haplogroups. Logistic regressions were performed to investigate diabetes duration and HbA1c as risk factors for PDR in the context of European mitochondrial haplogroups., Results: Neither diabetes duration nor HbA1c differed among mitochondrial haplogroups. Among DR patients from haplogroup H, longer diabetes duration and increasing HbA1c were significant risk factors for PDR (P = 0.0001 and P = 0.011, respectively). Neither diabetes duration nor HbA1c was a significant risk factor for PDR in DR patients from haplogroup UK., Conclusions: European mitochondrial haplogroups modify the effects of diabetes duration and HbA1c on PDR risk in patients with type 2 diabetes. In our patient population, longer diabetes duration and higher HbA1c increased PDR risk in patients from haplogroup H, but did not affect PDR risk in patients from haplogroup UK. This relationship has not been previously demonstrated and may explain, in part, why some patients with nonproliferative DR develop PDR and others do not, despite similar diabetes duration and glycemic control.

Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: We sought to examine regional and black-white differences in mean age at self-reported menopause among community-dwelling women in the United States., Study Design: This was a cross-sectional survey conducted in the context of the REasons for Geographic And Racial Differences in Stroke and Myocardial Infarction study., Results: We studied 22,484 menopausal women. After controlling for covariates, Southern women reported menopause 10.8 months earlier than Northeastern women, 8.4 months earlier than Midwestern women, and 6.0 months earlier than Western women (P < .05 for all). No difference was observed in menopausal age between black and white women after controlling for covariates (P = .69)., Conclusion: Women in the South report earlier menopause than those in other regions, but the cause remains unclear. Our study's large sample size and adjustment for multiple confounders lends weight to our finding of no racial difference in age at menopause. More study is needed of the implications of these findings with regard to vascular health., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: To determine racial differences in self-reported infertility and in risk factors for infertility in a cohort of black and white women., Design: A cross-sectional analysis of data from the longitudinal Coronary Artery Risk Development in Young Adults (CARDIA) Study, a prospective, epidemiologic investigation of the determinants and evolution of cardiovascular risk factors among black and white young adults and from the ancillary CARDIA Women's Study (CWS)., Setting: Population-based sample from four US communities (Birmingham, AL; Chicago, IL; Minneapolis, MN; Oakland, CA)., Patient(s): Women aged 33-44 years who had complete data (n = 764)., Intervention(s): None., Main Outcome Measure(s): Self-report of ever having unprotected sexual intercourse for at least 12 months without becoming pregnant., Result(s): Among nonsurgically sterile women, blacks had a twofold increased odds (95% confidence interval [CI] 1.3-3.1) of infertility compared with whites after adjustment for socioeconomic position (education and ability to pay for basics), correlates of pregnancy intent (marital status and hormonal contraceptive use), and risk factors for infertility (age, smoking, T, fibroid presence, and ovarian volume). The corresponding odds ratio among all women was 1.5 (95% CI 1.0-2.2). Difficulty paying for basics and ovarian volume were associated with infertility among black but not white women., Conclusion(s): In this population-based sample, black women were more likely to have experienced infertility. This disparity is not explained by common risk factors for infertility, such as smoking and obesity, and among nonsurgically sterile women, it is not explained by gynecologic risk factors such as fibroids and ovarian volume.

African-American (AA) women have earlier menarche on average than women of European ancestry (EA), and earlier menarche is a risk factor for obesity and type 2 diabetes among other chronic diseases. Identification of common genetic variants associated with age at menarche has a potential value in pointing to the genetic pathways underlying chronic disease risk, yet comprehensive genome-wide studies of age at menarche are lacking for AA women. In this study, we tested the genome-wide association of self-reported age at menarche with common single-nucleotide polymorphisms (SNPs) in a total of 18 089 AA women in 15 studies using an additive genetic linear regression model, adjusting for year of birth and population stratification, followed by inverse-variance weighted meta-analysis (Stage 1). Top meta-analysis results were then tested in an independent sample of 2850 women (Stage 2). First, while no SNP passed the pre-specified P < 5 × 10(-8) threshold for significance in Stage 1, suggestive associations were found for variants near FLRT2 and PIK3R1, and conditional analysis identified two independent SNPs (rs339978 and rs980000) in or near RORA, strengthening the support for this suggestive locus identified in EA women. Secondly, an investigation of SNPs in 42 previously identified menarche loci in EA women demonstrated that 25 (60%) of them contained variants significantly associated with menarche in AA women. The findings provide the first evidence of cross-ethnic generalization of menarche loci identified to date, and suggest a number of novel biological links to menarche timing in AA women.

Background: Uterine fibroids, the most common reproductive tract tumor in women, have been associated with hypertension and atherosclerotic cardiovascular disease (CVD). Prior studies of fibroids and CVD have examined the subset of women with symptomatic fibroids who undergo hysterectomy, itself a risk factor for CVD. We aimed to study the risk of subclinical CVD, as determined by coronary artery calcification (CAC), carotid intima media thickness (CIMT), and left ventricular (LV) mass, in women with ultrasound-diagnosed uterine fibroids. Materials and Methods: Participants were 972 women from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort recruited in 1985–1986. CARDIA screened black and white women aged 35–49 years by ultrasound for fibroids at 16 years of follow-up (2002–2004). Demographics and CVD risk factors were collected in 2000–2001 at 15 years of follow-up (baseline for this analysis). Women were tested at years 15, 20, and 25 for CAC, at year 20 for CIMT, and at year 25 for echocardiographic LV mass. Multivariable logistic regression was used to estimate the odds of CAC, CIMT, and LV mass. Results: Fifty-two percent of women had fibroids (61.7% in black, 38.3% in white women). Most CVD risk factors were more common in women with fibroids. Adjusted odds of subclinical CVD, such as elevated CIMT and elevated LV mass, were not different for women with fibroids compared with those without (CIMT odds ratio [OR] = 1.03; confidence interval [95% CI] 0.7–1.5 and LV mass OR = 1.14; 95% CI 0.77–1.68), when adjusted for confounders. Conclusions: Although women with fibroids had more CVD risk factors, presence of fibroids was not associated with subclinical CVD. [ABSTRACT FROM AUTHOR]

Background: Uterine fibroids (UF) affect 77% of women by menopause, and account for $9.4 billion in annual healthcare costs. Type-2-diabetes (T2D) has inconsistently associated with protection from UFs in prior studies. To further evaluate the relationship between T2D and UFs we tested for association between T2D and UF risk in a large clinical population as well as the potential differences due to T2D medications and interaction with race.Methods: This nested case-control study is derived from a clinical cohort. Our outcome was UF case-control status and our exposure was T2D. UF outcomes and T2D exposure were classified using validated electronic medical record (EMR) algorithms. Logistic regression, adjusted for covariates, was used to model the association between T2D diagnosis and UF risk. Secondary analyses were performed evaluating the interaction between T2D exposure and race and stratifying T2D exposed subjects by T2D medication being taken.Results: We identified 3,789 subjects with UF outcomes (608 UF cases and 3,181 controls), 714 were diabetic and 3,075 were non-diabetic. We observed a nominally significant interaction between T2D exposure and race in adjusted models (interaction p = 0.083). Race stratified analyses demonstrated more protection by T2D exposure on UF risk among European Americans (adjusted odds ratio [aOR] = 0.50, 95% CI 0.35 to 0.72) than African Americans (aOR = 0.76, 95% CI 0.50 to 1.17). We also observed a protective effect by T2D regardless of type of T2D medication being taken, with slightly more protection among subjects on insulin treatments (European Americans aOR = 0.42, 95% CI 0.26 to 0.68; African Americans aOR = 0.60, 95% CI 0.36 to 1.01).Conclusions: These data, conducted in a large population of UF cases and controls, support prior studies that have found a protective association between diabetes presence and UF risk and is further modified by race. Protection from UFs by T2D exposure was observed regardless of medication type with slightly more protection among insulin users. Further mechanistic research in larger cohorts is necessary to reconcile the potential role of T2D in UF risk. [ABSTRACT FROM AUTHOR]