Genomics of Reproductive Traits and Cardiometabolic Disease Risk in African American Women.

BACKGROUND: Age at menarche and age at natural menopause occur significantly earlier in African American women than in other ethnic groups. African American women also have twice the prevalence of cardiometabolic disorders related to the timing of these reproductive traits. OBJECTIVES: The objectives of this integrative review were to (a) summarize the genome-wide association studies of reproductive traits in African American women, (b) identify genes that overlap with reproductive traits and cardiometabolic risk factors in African American women, and (c) propose biological mechanisms explaining the link between reproductive traits and cardiometabolic risk factors. METHODS: PubMed was searched for genome-wide association studies of genes associated with reproductive traits in African American women. After extracting and summarizing the primary genes, we examined whether any of the associations with reproductive traits had also been identified with cardiometabolic risk factors in African American women. RESULTS: Seven studies met the inclusion criteria. Associations with both reproductive and cardiometabolic traits were reported in or near the following genes: FTO, SEC16B, TMEM18, APOE, PHACTR1, KCNQ1, LDLR, PIK3R1, and RORA. Biological pathways implicated include body weight regulation, vascular homeostasis, and lipid metabolism. DISCUSSION: A better understanding of the genetic basis of reproductive traits in African American women may provide insight into the biological mechanisms linking variation in these traits with increased risk for cardiometabolic disorders in this population.

Association of Obesity with DNA Methylation Age Acceleration in African American Mothers from the InterGEN Study.

African American women are affected by earlier onset of age-associated health deteriorations and obesity disproportionally, but little is known about the mechanism linking body mass index (BMI) and biological aging among this population. DNA methylation age acceleration (DNAm AA), measuring the difference between DNA methylation age and chronological age, is a novel biomarker of the biological aging process, and predicts aging-related disease outcomes. The present study estimated cross-tissue DNA methylation age acceleration using saliva samples from 232 African American mothers. Cross-sectional regression analyses were performed to assess the association of BMI with DNAm AA. The average chronological age and DNA methylation age were 31.67 years, and 28.79 years, respectively. After adjusting for smoking, hypertension diagnosis history, and socioeconomic factors (education, marital status, household income), a 1 kg/m2 increase in BMI is associated with 0.14 years increment of DNAm AA (95% CI: (0.08, 0.21)). The conclusion: in African American women, high BMI is independently associated with saliva-based DNA methylation age acceleration, after adjusting for smoking, hypertension, and socioeconomic status. This finding supports that high BMI accelerates biological aging, and plays a key role in age-related disease outcomes among African American women.

Improved gastrointestinal health for irritable bowel syndrome with metagenome-guided interventions.

Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder worldwide, and the most common reason for referral to gastroenterology clinics. However, the pathophysiology is still not fully understood and consequently current management guidelines are very symptom-specific, leading to mixed results. Here we present a study of 88 individuals with IBS who had baseline sequencing of their gut microbiome (stool samples), received targeted interventions that included dietary, supplement, prebiotic/probiotic, and lifestyle recommendations for a 30-day period, and a follow-up sequencing of their gut microbiome. The study's objectives were to demonstrate unique metagenomic signatures across the IBS phenotypes and to validate whether metagenomic-guided interventions could lead to improvement of symptom scores in individuals with IBS. Enrolled subjects also completed a baseline and post-intervention questionnaire that assessed their symptom scores. The average symptom score of an individual with IBS at baseline was 160 and at the endpoint of the study the average symptom score of the cohort was 100.9. The mixed IBS subtype showed the most significant reduction in symptom scores across the different subtypes (average decrease by 102 points, P = 0.005). The metagenomics analysis reveals shifts in the microbiome post-intervention that have been cross-validated with the literature as being associated with improvement of IBS symptoms. Given the complex nature of IBS, further studies with larger sample sizes, more targeted analyses, and a broader population cohort are needed to explore these results further.

Chronic Stress and Ovarian Function in Female Childhood Cancer Survivors.

OBJECTIVES: To explore the relationships among perceived stress, biomarkers of hypothalamic-pituitary-adrenal (HPA) activity, gonadotropin levels, and anti-Müllerian hormone (AMH) in female childhood cancer survivors (CCSs). SAMPLE & SETTING: 24 female CCSs from the Royal Hospital for Sick Children in Edinburgh, Scotland, were included in the study. METHODS & VARIABLES: Perceived stress was measured using the Perceived Stress Scale. HPA activity was measured using salivary cortisol and hair cortisol. Ovarian function was measured using serum gonadotropin levels and serum AMH levels. Latent growth curve modeling was used to determine diurnal cortisol slope and intercept. Bayesian structural equation modeling was used to explore the relationship among perceived stress, biomarkers of HPA activity, and ovarian function. RESULTS: The authors found an inverse association between perceived stress and ovarian function and a positive association between biomarkers of HPA activity and ovarian function. IMPLICATIONS FOR NURSING: Further research is needed to understand factors contributing to risk for post-treatment reproductive dysfunction in female CCSs.

Exploring the Ovarian Reserve Within Health Parameters: A Latent Class Analysis.

The process of ovarian aging is influenced by a complex and poorly understood interplay of endocrine, metabolic, and environmental factors. The purpose of this study was to explore the feasibility of using latent class analysis to identify subgroups based on cardiometabolic, psychological, and reproductive parameters of health and to describe patterns of anti-Müllerian hormone levels, a biomarker of the ovarian reserve, within these subgroups. Sixty-nine lean (body mass index [BMI] ⩽ 25 kg/m2) and severely obese (BMI ⩾ 40 kg/m2) postpartum women in Edinburgh, Scotland, were included in this exploratory study. The best fitting model included three classes: Class 1, n = 23 (33.5%); Class 2, n = 30 (42.2%); Class 3, n = 16 (24.3%). Postpartum women with lower ovarian reserve had less favorable cardiometabolic and psychological profiles. Examining the ovarian reserve within distinct subgroups based on parameters of health that affect ovarian aging may facilitate risk stratification in the context of ovarian aging.

Anti-Müllerian Hormone Levels and Urinary Cortisol in Women With Chronic Abdominal Pain.

OBJECTIVE: To explore the association of hypothalamic-pituitary-adrenal activity with ovarian functioning in women with and without chronic abdominal pain (CAP). DESIGN AND SETTING: A secondary data analysis was performed with data from female participants in a natural history protocol at the National Institutes of Health. PARTICIPANTS: A total of 36 women (age range = 19-39 years, mean = 27.11 years) were included in the study. METHODS: This pilot study was conducted with a subset of participants enrolled in a natural history protocol conducted in the Hatfield Clinical Research Center at the National Institutes of Health. The parent study included participants with and without CAP who provided a 5-hour urine sample for determination of cortisol levels and serum samples for determination of circulating levels of cortisol, luteinizing hormone, and follicle-stimulating hormone. CAP was defined as presence or absence of chronic pain for at least 6 months and was determined via self-report. RESULTS: Anti-Müllerian hormone (AMH) concentrations declined significantly with age as expected. When AMH levels were dichotomized as normal or abnormal (defined as higher or lower than age-specific normative ranges, respectively), there were significant associations between abnormal AMH levels and CAP and urine cortisol levels. Participants with CAP or low urine cortisol levels were significantly more likely to have abnormal AMH levels. CONCLUSION: Results suggest that chronic abdominal pain and hypothalamic-pituitary-adrenal dysregulation may be associated with abnormal AMH levels.