Risk Of Endometriosis Research Articles

A cross-sectional study on the relationship between dietary fiber and endometriosis risk based on NHANES 1999–2006

A cross-sectional study on the relationship between dietary fiber and endometriosis risk based on NHANES 1999–2006

Association between triglyceride glucose index and endometriosis in adults in the United States: A comprehensive study from the National Health and Nutrition Examination Survey (NHANES).

The triglyceride glucose (TyG) index has been well recognized as a reliable marker of insulin resistance and substantially correlated with the pathogenesis and progression of hypertension and cardiovascular diseases. However, no study has investigated the association between the TyG index and endometriosis. Therefore, this study aimed to uncover an association between the TyG index and endometriosis. This cross-sectional investigation employed the extensive dataset derived from the National Health and Nutrition Examination Survey (NHANES) (1999-2006). To explore the potential connection between the TyG and endometriosis, a multivariate weighted logistic regression model was established. The nonlinear relationship between the TyG index and the risk of endometriosis was explored using restricted cubic spline models (RCS). Furthermore, subgroup analyses were conducted. Ultimately, 2,508 individuals were included in this investigation. The findings unveiled a robust positive correlation between the TyG index and the susceptibility to endometriosis (OR [95% CI]: 1.52 [1.024,2.258]; P < 0.05). This positive association remained consistent across diverse subgroups. Age, birthplace, and whether one ovary was removed were identified as significant risk factors. In RCS analysis, the TyG index showed a nearly linear relationship with the risk of endometriosis (P-nonlinear > 0.05). The findings indicate a positive association between the TyG index and the risk of endometriosis, exhibiting an approximate non-linear relationship.

The association between vitamin intake and endometriosis: a cross-sectional study of the NHANES 1999–2006

BackgroundEndometriosis is a common cause of female reproductive problems, and vitamin intake may affect its incidence. Therefore, we further explored the association between multivitamin intake and endometriosis in a large population-based study.MethodsThis study included 3351 participants from the National Health and Nutrition Examination Survey (NHANES) 1999–2006. The dietary intake of eight vitamins was calculated as the average of two 24-h recall interviews, and information on endometriosis was obtained through questionnaires that included gynecological history. Multiple logistic regression analysis was used to explore the relationship between multivitamin intake and endometriosis. Smoothed curve fitting analysis was employed to assess the dose–response relationship between vitamins and endometriosis. Finally, subgroup analysis and interaction tests were conducted to determine the association of covariates between vitamins and endometriosis.ResultsIn this large-scale cross-sectional study, multiple logistic regression analysis showed that the intake of vitamins A, B1, B2, B6, C and folate was negatively associated with the occurrence of endometriosis. The odds ratios associated with a per-SD increase were 0.836 (95%CI: 0.702, 0.997), 0.817 (95%CI: 0.702, 0.951), 0.860 (95%CI: 0.746, 0.991), 0.784 (95%CI: 0.669, 0.919), 0.845 (95%CI: 0.718, 0.994), and 0.772 (95%CI: 0.660, 0.903), respectively. Smoothed curve fitting analysis revealed that the intake of vitamins A, B1, B2, B6, C, and folate was negatively associated with the risk of endometriosis (P < 0.05). Vitamin E showed a saturating effect, with an optimal cutoff point at 13.18. Below this cutoff, the intake of vitamin E was negatively correlated with the risk of endometriosis (OR = 0.947, 95% CI: 0.906, 0.989), whereas above the cutoff, there was no significant correlation between vitamin E intake and the risk of endometriosis (OR = 1.001, 95% CI: 0.997, 1.005).ConclusionsThe results of this study indicate a significant linear negative correlation between the intake of vitamins A, B1, B2, B6, C, and folate, and the risk of endometriosis, and reveal a threshold effect for vitamin E intake on the risk of endometriosis. These findings could inform clinical dietary interventions and may support the development of preventive strategies for endometriosis, potentially aiding in its reduction.

Inflammatory Bowel Disease and Endometriosis: Diagnosis and Clinical Characteristics

Background/Objectives: Endometriosis and inflammatory bowel disease (IBD) share some epidemiological, clinical and pathogenetic features. A differential diagnosis between pelvic endometriosis and IBD may be challenging, even for expert clinicians. In the present review, we aimed to summarize the currently available data regarding the relationship between endometriosis and IBD and their possible association. Methods: The PubMed and Scopus database were considered, by searching the following terms: “Crohn’s Disease”, “Ulcerative Colitis”, “Endometriosis”, “Adenomyosis”, and “Inflammatory Bowel Disease”, individually or combined. Full-text papers published in English with no date restriction were considered. Results: Few studies have researched the possible association between endometriosis and IBD. Both conditions are characterized by chronic recurrent symptoms, which may be shared (abdominal pain, fatigue, infertility, menstrual irregularities, diarrhea, constipation). Deep infiltrating endometriosis (DIE) can cause bowel symptoms. In a large Danish study, a 50% increased risk of IBD was observed in women with endometriosis. A missed diagnosis of endometriosis and an increased risk of endometriosis has been reported in IBD. Current evidence does not support an association between endometriosis and IBD characteristics. However, IBD may be associated with DIE, characterized by pelvic symptoms (dyschezia, dyspareunia). Preliminary observations suggest an increased IBD risk in patients with endometriosis treated with hormonal therapy. Conclusions: Current findings suggest that a careful search is needed for concomitant endometriosis in subgroups of patients with IBD showing compatible symptoms and vice versa. A multidisciplinary approach including dedicated gastroenterologists and gynecologists is required for a proper search for IBD and endometriosis in subgroups of patients. This approach may avoid diagnostic delays or overtreatments for these conditions.

Association Between Composite Dietary Antioxidant Index and Endometriosis from NHANES 2001-2006: A Cross-Sectional Study.

To evaluate the association between Composite Dietary Antioxidant Index (CDAI) and the risk of endometriosis in American women. The study adopted a cross-sectional design, incorporating 3862 women aged over 20 years, selected from the National Health and Nutrition Examination Survey (NHANES) dataset from 2001 to 2006. Six dietary antioxidants were taken into account in calculating CDAI. Endometriosis was determined based on self-report. To evaluate the association between CDAI and the risk of endometriosis, we employed models with multivariable logistic variables. For subgroup assessment in relation to CDAI, a stratified multivariate logistic regression model was utilized. Among all participants, 273 participants (7.1%) were found to exhibit endometriosis. The preliminary analysis showed a reverse association between CDAI and the likelihood of endometriosis (odds ratio [OR] = 0.95; 95% confidence interval [CI]: 0.92~0.98). Upon full adjustment within the multivariable logistic regression, the ORs (95% CI) for endometriosis prevalence per unit increase in CDAI were estimated to be 0.96 (0.93~1). When the CDAI levels were divided into quartiles, it was found that the ORs for endometriosis with CDAI levels in Q2 (-2.131-0.023), Q3 (0.023-2.650), and Q4 (2.650-42.854) were 0.74 (0.52, 1.05), 0.76 (0.53, 1.1), and 0.53 (0.36, 0.79), respectively, compared to those with CDAI levels in Q1 (-7.151--2.131). We evaluated the association between CDAI and endometriosis using subgroups stratified by age, race/ethnicity, education level, body mass index (BMI), oral contraceptive, and menopausal status, revealing a substantial negative relationship. In this cross-sectional study, increasing CDAI was proportionally associated with a reduced risk of endometriosis among American women, suggesting a diet high in antioxidants may play an important role in reducing the risk of endometriosis. The findings of NHANES data spanning 2001 to 2006 suggest that promoting antioxidant-rich diets could be an important prevention strategy for endometriosis.

The causal role of gastroesophageal reflux disease in endometriosis: a bidirectional Mendelian randomization study.

Observational studies have reported an association between gastroesophageal reflux disease (GERD) and endometriosis. We conducted a two-sample and bidirectional Mendelian randomization analysis to determine whether those associations are causal. Two-sample and bidirectional MR analyses were performed using summary statistics from the European Individual Genome-Wide Association Study (GWAS). The inverse variance weighting (IVW) method is used as the main analysis method to evaluate causality. Sensitivity analyses were performed to assess heterogeneity, horizontal versatility, and stability. The results showed no significant causal association between GERD in women with endometriosis in the UK Bank database [ratio (OR) ≈ 0, 95% adjusted interval (CI) 1.0007∼1.0044, P = 0.006] and Finn databases [ratio (OR) = 1.29, 95% adjusted interval (CI) 0.99∼1.67, P = 0.06]. However, when studying the Finn database only for endometriosis, which is confined to the uterus, a significant increase in GERD was limited to the risk of endometriosis in the uterus [ratio (OR) = 1.47, 95% adjusted interval (CI) 1.00∼2.17, P = 0.05]. Sensitivity analysis showed that the results were robust and did not detect multi efficacy or heterogeneity. Meanwhile, reverse MR analysis showed that endometriosis did not increase the risk of GERD. This MR study supports a causal relationship between GERD and an increased risk of endometriosis confined to the uterus. Therefore, patients with gastric esophageal reflux should be treated with gynecological examination to avoid and prevent the development of endometriosis.

Causality of immune cells and endometriosis: a bidirectional mendelian randomization study

BackgroundEndometriosis, a prevalent chronic condition, afflicts approximately 10% of women in their reproductive years. Emerging evidence implicates immune cells in the pathogenesis of endometriosis, particularly in angiogenesis, tissue proliferation, and lesion invasion. This investigation employs two-sample Mendelian Randomization (MR) to dissect the bidirectional causal relationships between immune cell profiles and endometriosis.MethodsWe leveraged publicly available genome-wide association study (GWAS) data to elucidate the causal interplay between immune cell traits and endometriosis. Utilizing GWAS summary statistics ranging from accession numbers GCST90001391 to GCST90002121 and endometriosis data from the FinnGen study GWAS (8,288 endometriosis cases and 68,969 controls), we adopted stringent criteria for instrumental variable selection. We applied MR-Egger, weighted median, inverse variance weighted (IVW), and weighted mode methods to derive causal estimates. To address potential heterogeneity and pleiotropy, Cochran’s Q test, MR-Egger intercept, and leave-one-out analyses were executed. Reverse-direction MR and bidirectional MR analyses evaluated potential reciprocal causation and the influence of endometriosis on immune cell composition.ResultsOur analysis identified five immune phenotypes inversely associated with endometriosis risk. These phenotypes comprise: a percentage of CD11c + HLA-DR + + monocytes, CD25 expression on CD39 + CD4 + T cells, elevated CD25 on CD45RA + CD4 + non-regulatory T cells, HLA-DR intensity on HLA-DR + CD8 bright (CD8br) T cells, and the proportion of naïve double-negative (CD4 − CD8− %DN) T cells. In contrast, eleven phenotypes were positively correlated with endometriosis risk, including: CD127 expression on T cells, the proportion of CD24 + CD27 + B cells within lymphocytes, CD25 expression on CD28 + CD4 + T cells, CD28 expression on CD39 + activated regulatory T cells (activated Tregs), the frequency of bright CD33 HLA-DR + CD14 − cells within the CD33br HLA-DR + compartment, CD45 expression on lymphocytes and natural killer (NK) cells, activation status of central memory CD8 bright (CM CD8br) T cells, CX3CR1 expression on monocytes, and the percentage of HLA-DR + NK cells within the NK cell subset. Sensitivity assessments that excluded significant heterogeneity and pleiotropy confirmed the stability of these associations, thereby reinforcing the validity of our findings.ConclusionThis study provides novel evidence of the potential causal impact of specific immune cells on the risk of developing endometriosis. These findings enhance our understanding of endometriosis pathophysiology and may inform innovative approaches for its diagnosis and management. While our findings provide novel insights, limitations such as potential horizontal pleiotropy and reliance on European ancestry data should be considered. Future research should expand to diverse populations and incorporate individual-level data to refine these findings.

Cross-Tissue Regulatory Network Analyses Reveal Novel Susceptibility Genes and Potential Mechanisms for Endometriosis

Endometriosis (EMT) is a common gynecological disease with a strong genetic component, while its precise etiology remains elusive. This study aims to integrate transcriptome-wide association study (TWAS), Mendelian randomization (MR), and bioinformatics analyses to reveal novel putatively causal genes and potential mechanisms. We obtained summary-level data of the Genotype-Tissue Expression Project (GTEx), v8 expression quantitative loci (eQTL) data, and the genome-wide association study (GWAS) data of EMT and its subtypes from the R11 release results of the FinnGen consortium for analysis. GWAS data of modifiable risk factors were collected from IEU Open GWAS. Cross-tissue TWAS analyses were performed using the unified test for molecular signature (UTMOST), while functional summary-based imputation (FUSION) was employed for single-tissue TWAS analyses. Furthermore, we also conducted multi-marker analysis of genomic annotation (MAGMA) analyses to validate the significant associations. Subsequent Mendelian randomization (MR) and colocalization analysis elucidated the causal associations between the identified genes across various tissues and EMT. To further delve into mechanisms, two-sample network MR analyses were conducted. At last, bioinformatics analyses were employed to enhance our understanding of the functional implications and expression patterns of these identified genes. For EMT, 22 significant gene signals were identified by UTMOST, 615 by FUSION, and 354 by MAGMA. Ultimately, six genes, including CISD2, EFRB, GREB1, IMMT, SULT1E1, and UBE2D3, were identified as candidate susceptibility genes for EMT. Through similar procedures, we identified GREB1, IL1A, and SULT1E1 for EMT of the ovary, and we identified GREB1 for EMT of the pelvic peritoneum, EMT of rectovaginal septum and vagina, and deep EMT. In MR analyses, the expression of IMMT in 21 tissues, EFR3B in the adrenal gland, CISD2 in 17 tissues, and UBE2D3 in 7 tissues demonstrated causal relationships with EMT risk. In addition, CISD2, IMMT, and UBE2D3, across different tissues, exhibited strong colocalization with EMT (PPH4 &gt; 0.7). Two-sample network MR analyses revealed that CISD2, EFR3B, and UBE2D3 could potentially regulate the levels of blood lipids and hip circumference so as to influence the risk of EMT. Furthermore, bioinformatics analyses confirmed our findings and delved into the biological functions of the identified genes. Our study unveiled seven novel candidate genes whose predicted expression was associated with the risk of EMT, providing new insights into the underlying genetic framework of EMT. These findings will facilitate a deeper comprehension of the tissue-specific transcriptional regulatory mechanisms associated with EMT, paving the way for optimizing the management and treatment of EMT.

Exploring the link between dietary zinc intake and endometriosis risk: insights from a cross-sectional analysis of American women

BackgroundEndometriosis is a complex disorder with genetic, immune, inflammatory, and multifactorial etiologies. Zinc, an essential trace element, plays a crucial role in various physiological processes. Dysregulation or deficiency of zinc can lead to aberrations in human physiology. However, the association between dietary zinc and endometriosis remains ambiguous. This study aimed to investigate the link between dietary zinc intake and endometriosis.MethodsUtilizing cross-sectional data from the National Health and Nutrition Examination Survey, we analyzed information from American women aged 20–54 years between 1999 and 2006. After adjusting for relevant covariates, multivariable logistic regression analysis was employed to assess correlations.ResultsA total of 4315 women were included in the study. The multivariable logistic regression model revealed a positive correlation between dietary zinc intake and the risk of endometriosis, even after controlling for confounding variables. Relative to individuals with lower zinc consumption (≤ 8 mg/day), the adjusted odds ratio (OR) values for dietary zinc intake and endometriosis in the 8–14 mg/day and > 14 mg/day groups were 1.19 (95% CI: 0.92–1.54, p = 0.189) and 1.60 (95% CI: 1.12–2.27, p = 0.009), respectively.ConclusionsOur findings suggest a positive correlation between dietary zinc intake and the prevalence of endometriosis. However, further investigations are necessary to better understand this association and explore the potential role of dietary zinc in endometriosis.

Beyond reproductive health: the cardiovascular risks of endometriosis.

Beyond reproductive health: the cardiovascular risks of endometriosis.

Circulating micronutrients levels and their association with the risk of endometriosis.

Endometriosis, a prevalent gynecological disease, has an unclear pathogenesis. Micronutrients play a crucial role in disease development, which has led to an investigation of their association with endometriosis. In this study, we analyzed the relationship between 15 micronutrients and endometriosis using both univariate and multivariate Mendelian randomization (MR) to assess the correlation. The results were validated using high-performance liquid chromatography (HPLC). The univariate MR analysis indicated that vitamin B6 (OR = 1.7060, 95% CI: 1.1796-2.4672, p = 0.0045) and calcium (OR = 1.4834, 95% CI: 1.0747-2.0475, p = 0.0165) are associated with an increased risk of endometriosis. Higher intakes of vitamin B6 and calcium are associated with a greater likelihood of developing endometriosis. The MR Egger regression's intercept term demonstrated no evidence of pleiotropy (p > 0.05) or heterogeneity (p > 0.05) in the SNPs for calcium and vitamin B6. In multivariate MR analysis, vitamin B6 (OR = 2.397, 95% CI: 1.231-4.669, p = 0.01) was linked to an increased risk of endometriosis, independently of other exposure factors. No significant heterogeneity (p = 0.831) or pleiotropy (p = 0.369) was observed in the genetic variation of endometriosis, affirming the reliability of the multivariate MR analysis. HPLC confirmed a significant increase in serum levels of vitamin B6 and calcium, aligning with the MR analysis findings. Vitamin B6 and calcium may be associated with this disease, with vitamin B6 potentially acting as an independent risk factor. Further research is essential to elucidate the role of micronutrients in disease, offering novel insights for prevention and treatment strategies.

Association between dietary vitamin B6 intake and endometriosis risk: evidence from the national health and nutrition examination survey.

Endometriosis is a multifaceted disorder with genetic, immune, inflammatory, and multifactorial origins. Vitamin B6 serves as a pivotal coenzyme in various metabolic pathways involving lipids, hemes, nucleic acids, proteins, and carbohydrates. Dysregulation or deficiency of vitamin B6 can perturb human physiology. However, the relationship between dietary vitamin B6 and endometriosis remains elusive. This study aims to explore how dietary intake of vitamin B6 is associated with the risk of endometriosis. Using cross-sectional data from the National Health and Nutrition Examination Survey, we analyzed information from American women aged 20-54 years between 1999 and 2006. After adjusting for relevant covariates, multivariable logistic regression analysis was employed to evaluate correlations. A total of 4,453 women were included in the study. The multiple linear regression model revealed a positive association between dietary vitamin B6 intake and the risk of endometriosis, even after controlling for confounding variables. Compared to individuals with lower vitamin B6 consumption (Q1: <0.94 mg/day), the adjusted odds ratio (OR) values for dietary vitamin B6 intake and endometriosis in Q2 (0.95-1.39 mg/day), Q3 (1.40-1.99 mg/day), and Q4 (>1.90 mg/day) were 1.22 (95% CI: 0.88-1.69, p = 0.23), 1.22 (95% CI: 0.86-1.73, p = 0. 279), and 1.51 (95% CI, 1.01-2. 24, p = 0.04), respectively. Our findings suggest a positive correlation between endometriosis and dietary vitamin B6 intake. Further investigations are imperative to establish a causal relationship between dietary vitamin B6 intake and endometriosis.

Association between cardiometabolic Index (CMI) and endometriosis: a cross-sectional study on NHANES

BackgroundEndometriosis is intricately linked to metabolic health. The Cardiometabolic Index (CMI), a novel and readily accessible indicator, is utilized to evaluate metabolic status. This study seeks to investigate the potential correlation between CMI and endometriosis.MethodsData from four consecutive survey cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2006 were utilized. This included adult females with self-reported diagnoses of endometriosis and complete information required for calculating the CMI. The calculation formula for CMI is Triglycerides(TG) / High-density lipoprotein cholesterol (HDL-C) × WHtR (WHtR = waist circumference / height). A multivariable logistic regression model was employed to investigate the linear association between CMI and endometriosis. Subgroup analyses were performed to explore potential influencing factors. Additionally, the linear relationship was validated using restricted cubic spline (RCS) curve plotting and threshold effect analysis.ResultsThis study, based on the National Health and Nutrition Examination Survey (NHANES), included a cohort of 2,224 adult women. The multivariable logistic regression analysis demonstrated that in the fully adjusted model, individuals with the highest CMI exhibited a 78% elevated likelihood of endometriosis compared to those with the lowest CMI (OR = 1.78; 95% CI, 1.02–3.11, P < 0.05). The subgroup analysis indicated that there were no significant interactions between CMI and specific subgroups (all interaction P > 0.05), except for the subgroup stratified by stroke status (P < 0.05). Additionally, the association between CMI and endometriosis was linear, with a 20% increase in the association for each unit increase in CMI when CMI > 0.67 (OR = 1.20; 95% CI, 1.05–1.37, P < 0.01).ConclusionThe study found that CMI levels are closely correlated with endometriosis, with this correlation increasing when the CMI exceeds 0.67. This finding implies that by regularly monitoring CMI levels, physicians may be able to screen women at risk for endometriosis at an earlier stage, thereby enabling the implementation of early interventions to slow the progression of the disease. To further validate these findings, larger-scale cohort studies are required to support the results of this research.

Bidirectional Mendelian Randomization Reveals Causal Effects of Immune Cell Traits on Endometriosis Risk.

Previous studies have identified associations between immune cell traits and endometriosis, but the causality of these relationships remains uncertain. In this study, we utilized Mendelian randomization (MR) to investigate the causal relationship between immune cell traits and endometriosis for the first time. Seven hundred and thirty-one immune cell signatures associated with single-nucleotide polymorphisms (SNPs) were extracted from a published genome-wide association study (GWAS) involving 472174 individuals, while endometriosis data, including four stages and seven subtypes, were obtained from the FinnGen consortium. Four methods were used for MR. The causal effect of immune cell traits on endometriosis was explored after Bonferroni correction. Significant causal relationship included 92 immune cell traits distributed among B cell (28 cells), cDC (2 cells), maturation stages of T cell (10 cells), monocyte (12 cells), Myeloid cell (5 cells), TBNK (13 cells), and Treg panels (22 cells). One of the most significant findings is that for every 1-standard deviation (SD) increase in CD8 on Central Memory CD8+ T cell, the risks of developing endometriosis of the fallopian tube increased by 72%. In the reverse MR analysis, a one-unit increase in the log odds of endometriosis of the ovary risk corresponded to a decrease in the absolute count of CD4+ CD8dim T cell by 0.10. This study represents the first comprehensive evaluation of the causal effects of immune cell traits on the risk/protection of different stages/subtypes of endometriosis. The findings highlight the complex and significant role of immune-derived factors in the pathogenesis of the disease.

Causal relationships between leukocyte telomere length and female reproductive system diseases: A bidirectional Mendelian randomization study

Objective: Although numerous observational studies have revealed a correlation between leukocyte telomere length (LTL) and female reproductive system diseases (RSDs), the findings of these studies have tended to be consistent. In this study, we accordingly sought to clarify the causal relationships between LTL and RSDs. Methods: We performed a bidirectional two-sample Mendelian randomization (MR) analysis using pooled statistics from genome-wide association studies of LTL and nine female RSDs. The final results were analyzed using five MR methods, with the inverse variance weighted (IVW) method used as the primary outcome. We applied MR-PRESSO to exclude outliers. Sensitivity analyses were also conducted to assess heterogeneity and pleiotropy. Results: In the forward MR analysis, a genetic prediction of longer LTLs was found to be causally associated with higher risks of endometriosis (IVW: OR = 1.25, 95%CI: 1.06–1.46, P = 0.008), leiomyoma of the uterus (IVW: OR = 1.73, 95%: 1.52–1.98, P = 4.9E-16) and ovarian cysts (IVW: OR = 1.31, 95%:1.19–1.45, P = 1.5E-07). In the reverse MR results, female RSDs were shown to have no significant effect on LTLs (all P-values &gt; 0.05). Sensitivity analysis confirmed the robustness of these results. Conclusions: Our findings substantiate the assumption that a genetically predicted longer LTL elevates the risk of endometriosis, leiomyoma of the uterus, and ovarian cysts, with no influence of RSDs on LTL. These findings contribute to establishing a causal link between LTL and RSDs, overcoming the constraints of earlier observational studies. They also imply that LTL could potentially serve as a biomarker for the occurrence of endometriosis, leiomyoma of the uterus, and ovarian cysts.

Causality between neuroticism personality clusters and female reproductive diseases in European population: a two-sample bidirectional mendelian randomization study

BackgroundThe causality between neuroticism, a personality trait characterized by the tendency to experience negative emotions, and female reproductive diseases remains unclear. To provide evidence for the development of effective screening and prevention strategies, this study employed Mendelian randomization (MR) to investigate the causality between neuroticism clusters and female reproductive diseases.MethodsInstrumental variables were obtained from large-scale genome-wide association studies of populations of European descent involving three neuroticism clusters (depressed affect, worry, sensitivity to environmental stress, and adversity [SESA]) in the Complex Trait Genetics database and six female reproductive diseases (infertility, polycystic ovary syndrome [PCOS], spontaneous abortion, recurrent spontaneous abortion, endometriosis, and uterine fibroids) in the FinnGen database. The bidirectional two-sample MR analysis was conducted using the inverse variance-weighted, weighted median, and MR-Egger methods, whereas the sensitivity analysis was conducted using the Cochran’s Q-test, MR-Egger intercept, and leave-one-out analysis.ResultsIn the forward analysis, genetically predicted depressed affect and worry components of neuroticism significantly increased the risk of infertility (depressed affect: odds ratio [OR] = 1.399, 95% confidence interval [CI]: 1.054–1.856, p = 0.020; worry: OR = 1.587, 95% CI: 1.229–2.049, p = 0.000) and endometriosis (depressed affect: OR = 1.611, 95% CI: 1.234–2.102, p = 0.000; worry: OR = 1.812, 95% CI: 1.405–2.338, p = 0.000). Genetically predicted SESA component of neuroticism increased only the risk of endometriosis (OR = 1.524, 95% CI: 1.104–2.103, p = 0.010). In the reverse analysis, genetically predicted PCOS was causally associated with an increased risk of the worry component of neuroticism (Beta = 0.009, 95% CI: 0.003–0.016, p = 0.003).ConclusionsThe MR study showed that the three neuroticism personality clusters had definite causal effects on at least one specific female reproductive disease. Moreover, PCOS may increase the risk of the worry component of neuroticism. This finding suggests the need to screen for specific female reproductive diseases in populations with high neuroticism and assess the psychological status of patients with PCOS.

Concurrent detection of the mitochondrial DNA copy number and the +35G/C polymorphism in the mitochondrial transcription factor A gene in endometriosis

Background and aimEndometriosis is a chronic gynecological inflammatory disease. The mitochondrial DNA copy number (mtDNA CN) and mitochondrial transcription factor A (TFAM) are known to contribute to human pathologies and cancer. Therefore, this study aims to reveal the association of mtDNA CN and TFAM+35G/C (rs1937) polymorphism with the risk of endometriosis in Egyptian females. Materials and methodsThis case-control study involved 160 Egyptian females divided into two groups: 80 endometriosis cases and 80 controls. The mtDNA CN was quantified using a real-time quantitative PCR (qPCR), and the TFAM +35G/C SNP (rs1937) was genotyped using the TaqMan allelic discrimination assay technique. ResultsThe mtDNA CN was markedly decreased in endometriosis cases compared to controls (P < 0. 001). TFAM rs1937 genotypes and allele distributions were all in Hardy-Weinberg equilibrium. The GC genotype and the ‘C’ allele frequency (P = 0.015 and P = 0.017, respectively) were substantially greater in endometriosis cases. ConclusionDecreased mtDNA CN and the GC genotype of TFAM +35G/C polymorphism were significantly associated with the risk of endometriosis in Egyptian females.

Exploring the causal associations between diet-derived circulating antioxidants and the risk of endometriosis: a Mendelian randomization study.

Numerous observational studies and randomized controlled trials have recently revealed the associations between circulating antioxidants and the risk of endometriosis, while the underlying causal relationship remains unclear. This study aimed to investigate the causal association between genetically determined circulating antioxidants and the risk of endometriosis using Mendelian randomization (MR). A two-sample MR analysis was conducted using publicly available summary data from genome-wide association studies (GWAS) to investigate the causal impact of genetically determined absolute circulating antioxidants (such as ascorbate, retinol, β-carotene, and lycopene) and their metabolites (including α-and γ-tocopherol, ascorbate, and retinol) on the risk of endometriosis. The study used inverse variance weighted (IVW) or Wald ratio analyses as the primary estimation method and also conducted sensitivity analyses to assess heterogeneity and pleiotropy. No significant causality was observed for genetically determined circulating antioxidants and the risk of endometriosis. The pooled odds ratios (ORs) for absolute circulating antioxidants were 0.62 (95% CI: 0.32-1.18, retinol), 0.95 (95% CI: 0.79-1.15, β-carotene), 1.01 (95% CI: 0.95-1.08, lycopene), and 1.00 (95% CI: 0.99-1.02, ascorbate, expressed as a Wald ratio). The pooled ORs indicating the EM risk per unit increase in circulating antioxidant metabolites were 1.04 (95% CI: 0.82-1.33, γ-tocopherol), 0.91 (95% CI: 0.57-1.46, α-tocopherol), 1.03 (95% CI: 0.99-1.07, retinol), and 0.96 (95% CI: 0.87-1.06, ascorbate). Our study demonstrated that increased levels of diet-derived circulating antioxidants were not significantly associated with a reduced risk of endometriosis.

Enhancing genetic association power in endometriosis through unsupervised clustering of clinical subtypes identified from electronic health records.

Endometriosis is a complex and heterogeneous condition affecting 10% of reproductive-age women, and yet, it often goes undiagnosed for several years. Limited observed heritability (7%) of large genetic association studies may be attributable to underlying heterogeneity of disease mechanisms. Therefore, we conducted this study to investigate genetic associations across sub-phenotypes of endometriosis. We performed unsupervised clustering of 4,078 women with endometriosis based on known endometriosis risk factors, symptoms, and concomitant conditions. The clusters were characterized by examining electronic health record (EHR) data and comprehensive chart reviews. We then performed genetic association for each cluster with 39 endometriosis-associated loci (Total Nendometriosis cases = 12,350). We identified five sub-phenotype clusters: (1) pain comorbidities, (2) uterine disorders, (3) pregnancy complications, (4) cardiometabolic comorbidities, and (5) HER-asymptomatic. Bonferroni significant loci included PDLIM5 for the cluster 1, GREB1 for cluster 2, WNT4 for cluster 3, RNLS for cluster 4, and ABO for cluster 5. The difference in associations between the groups suggests complex and varied genetic mechanisms of endometriosis and its symptoms. This study enhances our understanding of the clinical patterns of endometriosis sub-phenotypes, showcasing the innovative approach employed to investigate this complex disease.

Causal Relationship Between Mood Swing and Gynecological Disorders: A Mendelian Randomization Study.

Gynecological disorders are a wide range of health problems affecting the female reproductive system, which poses substantial health challenges worldwide. Increasing number of observational studies have associated mood instability to common female diseases, but the underlying causal relationship remains unclear. In this work, Mendelian randomization (MR) analysis was applied to explore the genetically predicted causal relationship of mood swings and several prevalent gynecological disorders. Instrumental variables (IVs) of mood swings were selected from UK Biobank (UKB), with 204,412 cases and 247,207 controls being incorporated. The genetic variants for female disorders were obtained from genome-wide association studies (GWASs) and FinnGen consortium. To avoid biases caused by racial difference, only European population was included here. Five strong analytical methodologies were used to increase the validity of the results, the most substantial of which was the inverse variance weighting (IVW) method. Pleiotropy, sensitivity, and heterogeneity were assessed to strengthen the findings. We found mood swings was significantly positively associated with risk of endometrial cancer (OR= 2.60 [95% CI= 1.36, 4.95], P= 0.0037), cervical cancer (OR= 1.01[95% CI= 1.00,1.02], P= 0.0213) and endometriosis (OR= 2.58 [95% CI= 1.18, 5.60], P= 0.0170) by IVW method. However, there was no causal relationship between mood swing and ovarian cancer. No pleiotropy and heterogeneity existed and sensitivity tests were passed. This study reveals that mood swing may serve as a genetically predicted causal risk factor for endometrial cancer, cervical cancer, and endometriosis in the European population, while no such association was observed for ovarian cancer. These findings make up for observational research's inherent limitations and may improve patient outcomes in the field of gynecological health. However, the study's focus on European populations may limit the applicability of these results globally.