cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.30281147
title: Association analysis of MTHFR (C677T, A1298C) and MTRR (A66G) gene polymorphisms on susceptibility to gestational diabetes mellitus in Chinese pregnant women

description: Gestational diabetes mellitus (GDM) is a common pregnancy complication with rising incidence and adverse maternal-fetal outcomes. Genetic polymorphisms in folate metabolism genes may influence GDM susceptibility through homocysteine pathway alterations. To investigate the associations between MTHFR (C677T, A1298C) and MTRR (A66G) polymorphisms and GDM risk, including gene‒gene interactions, in Chinese Han pregnant women, this retrospective cohort study analyzed 1312 Chinese Han pregnant women. The MTHFR C677T, A1298C, and MTRR A66G polymorphisms were genotyped using allele-specific PCR. Polymorphism-GDM associations were assessed using logistic regression, adjusting for maternal age, prepregnancy BMI, and folate intake. Gene‒gene interactions were evaluated using multiplicative interaction models. After confounder adjustment, the MTHFR 677TT genotype was associated with GDM (OR 1.89, 95% CI 1.24−2.93) compared to wild-type. The MTRR 66AG and 66GG genotypes were associated with GDM, with ORs of 2.73 (95% CI: 1.93–3.89) and 3.10 (95% CI: 1.72–5.41), respectively. Significant gene‒gene interactions were observed between MTHFR C677T & A1298C (OR 2.22, 95% CI 1.25−4.23 for TT/AA combination) and MTHFR C677T & MTRR A66G (OR 6.06, 95% CI 3.48−14.10 for TT/AG combination), indicating synergistic effects that surpass the expected multiplicative combination of individual polymorphism effects. MTHFR C677T and MTRR A66G polymorphisms independently and interactively increase GDM odds in Chinese Han women, enabling personalized risk prediction and targeted prevention.
DOI: 10.6084/m9.figshare.30281147.v1
title: Association analysis of MTHFR (C677T, A1298C) and MTRR (A66G) gene polymorphisms on susceptibility to gestational diabetes mellitus in Chinese pregnant women

description: Gestational diabetes mellitus (GDM) is a common pregnancy complication with rising incidence and adverse maternal-fetal outcomes. Genetic polymorphisms in folate metabolism genes may influence GDM susceptibility through homocysteine pathway alterations. To investigate the associations between MTHFR (C677T, A1298C) and MTRR (A66G) polymorphisms and GDM risk, including gene‒gene interactions, in Chinese Han pregnant women, this retrospective cohort study analyzed 1312 Chinese Han pregnant women. The MTHFR C677T, A1298C, and MTRR A66G polymorphisms were genotyped using allele-specific PCR. Polymorphism-GDM associations were assessed using logistic regression, adjusting for maternal age, prepregnancy BMI, and folate intake. Gene‒gene interactions were evaluated using multiplicative interaction models. After confounder adjustment, the MTHFR 677TT genotype was associated with GDM (OR 1.89, 95% CI 1.24−2.93) compared to wild-type. The MTRR 66AG and 66GG genotypes were associated with GDM, with ORs of 2.73 (95% CI: 1.93–3.89) and 3.10 (95% CI: 1.72–5.41), respectively. Significant gene‒gene interactions were observed between MTHFR C677T & A1298C (OR 2.22, 95% CI 1.25−4.23 for TT/AA combination) and MTHFR C677T & MTRR A66G (OR 6.06, 95% CI 3.48−14.10 for TT/AG combination), indicating synergistic effects that surpass the expected multiplicative combination of individual polymorphism effects. MTHFR C677T and MTRR A66G polymorphisms independently and interactively increase GDM odds in Chinese Han women, enabling personalized risk prediction and targeted prevention.
DOI: 10.6084/m9.figshare.29847174
title: Premature ovarian insufficiency as a consequence of immunological abnormalities and dyslipidemia: a Mendelian randomization study

description: Observational studies have suggested associations between premature ovarian insufficiency (POI) and immunological abnormalities or dyslipidemia, but causal evidence remains unestablished. We conducted a two-sample Mendelian randomization (MR) study to evaluate causal relationships of POI with immune cell traits (CD4+ regulatory T cell [Treg], and its subtype CD39 + CD4+ Treg, CD33 expression) and lipid metabolism markers (low-density lipoprotein [LDL] and intermediate-density lipoprotein [IDL] subfractions). Genetic instruments were derived from three independent sources: immune cell data from 3,757 Sardinians, lipid traits from 21,559 Europeans, and POI cases (<i>N</i> = 655) with population-matched controls (<i>N</i> = 267,780) from FinnGen R12. Primary causal estimates were generated using inverse-variance weighted regression, complemented by sensitivity analyses (MR-Egger, MR-PRESSO). CD39+ Treg subpopulations showed robust protection against POI in proportional analyses: secreting (�4 Treg: OR = 0.889, <i>p</i> = 0.015), activated (�4 Treg: OR = 0.881, <i>p</i> = 0.021). CD39+ resting Treg absolute count was significant (OR = 0.861, <i>p</i> = 0.027), while CD39 expression on activated/secreting Treg reduced risk (OR = 0.917–0.904, <i>p</i> &lt; 0.05). Elevated CD33 expression on 9 of 12 myeloid cell subsets (e.g. granulocytic myeloid-derived suppressor Cells, CD33+ monocytes), and plasma CD33 protein (OR = 0.877, <i>p =</i> 0.030) were inversely associated with POI risk. Dyslipidemia traits demonstrated causal associations: total cholesterol (OR = 1.328, p = 0.028), large LDL-free cholesterol (OR = 1.28, p = 0.030), and IDL components—total cholesterol, free cholesterol, phospholipids, particle concentration, and total lipids (OR = 1.287–1.345, all p &lt; 0.05). This study establishes POI as an immunometabolic disorder driven by Tregs deficiency, CD33-mediated protection, and lipid dysregulation, advocating targeted therapies for ovarian protection.
DOI: 10.6084/m9.figshare.29847174.v1
title: Premature ovarian insufficiency as a consequence of immunological abnormalities and dyslipidemia: a Mendelian randomization study

description: Observational studies have suggested associations between premature ovarian insufficiency (POI) and immunological abnormalities or dyslipidemia, but causal evidence remains unestablished. We conducted a two-sample Mendelian randomization (MR) study to evaluate causal relationships of POI with immune cell traits (CD4+ regulatory T cell [Treg], and its subtype CD39 + CD4+ Treg, CD33 expression) and lipid metabolism markers (low-density lipoprotein [LDL] and intermediate-density lipoprotein [IDL] subfractions). Genetic instruments were derived from three independent sources: immune cell data from 3,757 Sardinians, lipid traits from 21,559 Europeans, and POI cases (<i>N</i> = 655) with population-matched controls (<i>N</i> = 267,780) from FinnGen R12. Primary causal estimates were generated using inverse-variance weighted regression, complemented by sensitivity analyses (MR-Egger, MR-PRESSO). CD39+ Treg subpopulations showed robust protection against POI in proportional analyses: secreting (�4 Treg: OR = 0.889, <i>p</i> = 0.015), activated (�4 Treg: OR = 0.881, <i>p</i> = 0.021). CD39+ resting Treg absolute count was significant (OR = 0.861, <i>p</i> = 0.027), while CD39 expression on activated/secreting Treg reduced risk (OR = 0.917–0.904, <i>p</i> &lt; 0.05). Elevated CD33 expression on 9 of 12 myeloid cell subsets (e.g. granulocytic myeloid-derived suppressor Cells, CD33+ monocytes), and plasma CD33 protein (OR = 0.877, <i>p =</i> 0.030) were inversely associated with POI risk. Dyslipidemia traits demonstrated causal associations: total cholesterol (OR = 1.328, p = 0.028), large LDL-free cholesterol (OR = 1.28, p = 0.030), and IDL components—total cholesterol, free cholesterol, phospholipids, particle concentration, and total lipids (OR = 1.287–1.345, all p &lt; 0.05). This study establishes POI as an immunometabolic disorder driven by Tregs deficiency, CD33-mediated protection, and lipid dysregulation, advocating targeted therapies for ovarian protection.
DOI: 10.6084/m9.figshare.30596076
title: Polycystic ovary syndrome: pragmatic management across levels of care

description: Polycystic ovary syndrome (PCOS) is a common endocrine condition requiring coordinated management across reproductive, metabolic, and psychological domains. This narrative review explores pragmatic strategies that can be applied across levels of care, considering workforce capacity, referral thresholds, and patient access. PubMed, Embase, and Ovid were searched (2000–2025) for guidelines, systematic reviews, clinical trials, and qualitative studies. Evidence was synthesised with attention to feasibility in primary versus secondary care. Menstrual irregularity can usually be managed in primary care with combined oral contraceptives or progestins, with referral for fertility or complex cases. Dermatological symptoms such as hirsutism and acne may require topical or hormonal therapy, with escalation to anti-androgens or dermatology input. Cardiometabolic and glycaemic risk should be screened routinely in general practice, with specialist referral for complex profiles. Emotional wellbeing—including anxiety, depression, eating disorders, and body image concerns—can be screened in primary care using validated questionnaires with onward referral as needed. Pragmatic PCOS care requires clear delineation between primary and specialist roles, integration of digital tools, and patient-centred education to reduce duplication, improve efficiency, and enhance outcomes.
DOI: 10.6084/m9.figshare.30596076.v1
title: Polycystic ovary syndrome: pragmatic management across levels of care

description: Polycystic ovary syndrome (PCOS) is a common endocrine condition requiring coordinated management across reproductive, metabolic, and psychological domains. This narrative review explores pragmatic strategies that can be applied across levels of care, considering workforce capacity, referral thresholds, and patient access. PubMed, Embase, and Ovid were searched (2000–2025) for guidelines, systematic reviews, clinical trials, and qualitative studies. Evidence was synthesised with attention to feasibility in primary versus secondary care. Menstrual irregularity can usually be managed in primary care with combined oral contraceptives or progestins, with referral for fertility or complex cases. Dermatological symptoms such as hirsutism and acne may require topical or hormonal therapy, with escalation to anti-androgens or dermatology input. Cardiometabolic and glycaemic risk should be screened routinely in general practice, with specialist referral for complex profiles. Emotional wellbeing—including anxiety, depression, eating disorders, and body image concerns—can be screened in primary care using validated questionnaires with onward referral as needed. Pragmatic PCOS care requires clear delineation between primary and specialist roles, integration of digital tools, and patient-centred education to reduce duplication, improve efficiency, and enhance outcomes.
DOI: 10.6084/m9.figshare.29205814
title: Dissecting the causal effects of interleukin receptor-related factors and the risk of developing endometriosis: a two-sample Mendelian randomization study

description: This study investigates the causal associations between interleukin receptor-related factors and the development of endometriosis, as their etiology and pathophysiology remain largely unknown. A two-sample Mendelian randomization (MR) approach was employed to analyze genetic variants associated with interleukin receptor related factors as instrumental variables (IVs). The F-values have to be &gt; 10 to exclude weak instrumental bias. The primary analysis was conducted using the inverse variance weighted (IVW) method, with confirmation using the MR-Egger, weighted median (WM), simple mode, and weighted mode methods. Sensitivity analyses were performed to ensure robustness, including tests for heterogeneity, pleiotropy, and leave-one-out. Multivariable MR (MVMR) analysis was used to assess the direct and mediated effects of immune cells. The results indicated significant causal associations between interleukin receptor factors prot-a-1542 (IL-6Rβ), prot-a-1530 (IL-3Rα), and prot-b-38 (IL-1RL1) and endometriosis. Reverse MR analysis showed that endometriosis did not significantly affect prot-a-1530 or prot-b-38. After adjusting for confounders like body mass index and smoking, these factors retained their significance. Additionally, immune cells(ebi-a-GCST90001951) were found to mediate the relationship between prot-b-38 and endometriosis, with an indirect effect accounting for approximately 6.38% of the total effect. This study provides new insights into endometriosis mechanisms involving specific interleukin receptor factors.
DOI: 10.6084/m9.figshare.29205814.v1
title: Dissecting the causal effects of interleukin receptor-related factors and the risk of developing endometriosis: a two-sample Mendelian randomization study

description: This study investigates the causal associations between interleukin receptor-related factors and the development of endometriosis, as their etiology and pathophysiology remain largely unknown. A two-sample Mendelian randomization (MR) approach was employed to analyze genetic variants associated with interleukin receptor related factors as instrumental variables (IVs). The F-values have to be &gt; 10 to exclude weak instrumental bias. The primary analysis was conducted using the inverse variance weighted (IVW) method, with confirmation using the MR-Egger, weighted median (WM), simple mode, and weighted mode methods. Sensitivity analyses were performed to ensure robustness, including tests for heterogeneity, pleiotropy, and leave-one-out. Multivariable MR (MVMR) analysis was used to assess the direct and mediated effects of immune cells. The results indicated significant causal associations between interleukin receptor factors prot-a-1542 (IL-6Rβ), prot-a-1530 (IL-3Rα), and prot-b-38 (IL-1RL1) and endometriosis. Reverse MR analysis showed that endometriosis did not significantly affect prot-a-1530 or prot-b-38. After adjusting for confounders like body mass index and smoking, these factors retained their significance. Additionally, immune cells(ebi-a-GCST90001951) were found to mediate the relationship between prot-b-38 and endometriosis, with an indirect effect accounting for approximately 6.38% of the total effect. This study provides new insights into endometriosis mechanisms involving specific interleukin receptor factors.
DOI: 10.6084/m9.figshare.28722222
title: Association between inflammatory biomarkers and gestational diabetes mellitus in women aged 20–44: a cross-sectional analysis of NHANES 2007–2018

description: Inflammation exerts an essential role in gestational diabetes mellitus (GDM), but the relationship between peripheral blood inflammatory markers and GDM remains unclear. The purpose of this study was to explore the relationship between inflammatory markers and GDM in US adults. Data were extracted from the National Health and Nutrition Examination Survey. Five inflammatory markers were derived from complete blood count. Survey-weighted multivariable logistic regression models were used to assess the association between inflammatory markers and GDM. Restricted cubic splines and subgroup analyses were conducted to validate the stability of the results. Finally, a total of 2363 women aged 20–44 were included based on specific criteria, with 229 self-reported GDM cases (9.69%). The increased lymphocyte–monocyte ratio (LMR) was associated with the higher risk of GDM, aOR = 1.82 (CI:1.30–2.56). Compared with the lowest tertile, the highest tertile group of LMR showed a significantly increased risk of GDM, aOR = 2.24 (CI: 1.28–2.85). Conversely, the highest tertile group of systemic inflammation response index (SIRI) was negatively associated with GDM, aOR = 0.61 (95% CI: 0.40–0.94). And high platelet–lymphocyte ratio (PLR) levels are related to a lower risk of GDM. No non-linear relationships were observed. Furthermore, subgroup analysis revealed that the association between LMR, SIRI, and GDM remained consistent with the overall results. Our study indicated that LMR, PLR, and SIRI may be potential predictors of GDM. Further large-scale prospective study is needed to investigate the role of LMR, PLR and SIRI in GDM.
DOI: 10.6084/m9.figshare.28722222.v1
title: Association between inflammatory biomarkers and gestational diabetes mellitus in women aged 20–44: a cross-sectional analysis of NHANES 2007–2018

description: Inflammation exerts an essential role in gestational diabetes mellitus (GDM), but the relationship between peripheral blood inflammatory markers and GDM remains unclear. The purpose of this study was to explore the relationship between inflammatory markers and GDM in US adults. Data were extracted from the National Health and Nutrition Examination Survey. Five inflammatory markers were derived from complete blood count. Survey-weighted multivariable logistic regression models were used to assess the association between inflammatory markers and GDM. Restricted cubic splines and subgroup analyses were conducted to validate the stability of the results. Finally, a total of 2363 women aged 20–44 were included based on specific criteria, with 229 self-reported GDM cases (9.69%). The increased lymphocyte–monocyte ratio (LMR) was associated with the higher risk of GDM, aOR = 1.82 (CI:1.30–2.56). Compared with the lowest tertile, the highest tertile group of LMR showed a significantly increased risk of GDM, aOR = 2.24 (CI: 1.28–2.85). Conversely, the highest tertile group of systemic inflammation response index (SIRI) was negatively associated with GDM, aOR = 0.61 (95% CI: 0.40–0.94). And high platelet–lymphocyte ratio (PLR) levels are related to a lower risk of GDM. No non-linear relationships were observed. Furthermore, subgroup analysis revealed that the association between LMR, SIRI, and GDM remained consistent with the overall results. Our study indicated that LMR, PLR, and SIRI may be potential predictors of GDM. Further large-scale prospective study is needed to investigate the role of LMR, PLR and SIRI in GDM.
DOI: 10.6084/m9.figshare.30390907
title: FGFR1-related congenital hypogonadotropic hypogonadism: a case report and literature review

description: Congenital hypogonadotropic hypogonadism (CHH) is a rare condition characterized by incomplete pubertal development, infertility, and gonadotropin-releasing hormone deficiency, associated with mutations in more than 50 genes. We aimed to conduct an etiological analysis of a CHH Chinese family and summarize the clinical presentations and genetic changes of reported similar cases. Whole-exome sequencing (WES) was performed to identify the molecular cause in the proband. In silico tools were employed to analyze the pathogenicity of the variants. Reported cases with similar clinical features and associated genes were summarized by searching through PubMed/MEDLINE using keywords ‘FGFR1,’ ‘CHH,’ and ‘Kallmann syndrome (KS).’ Genetic analysis revealed a novel likely pathogenic deletion mutation in the FGFR1 gene (NM_023110.3: c.263_264del (Val88Alafs*22)) in a Chinese family exhibiting micropenis and underdeveloped testes. A total of 38 cases with CHH or KS have been previously reported. This study identified a novel FGFR1 deletion variant responsible for CHH, expanding the known mutational spectrum of FGFR1. Typical manifestations include delayed puberty and diverse presentations. The genotype–phenotype correlation in CHH remains unclear and may involve oligogenic effects and epigenetic regulation.
DOI: 10.6084/m9.figshare.30390907.v1
title: FGFR1-related congenital hypogonadotropic hypogonadism: a case report and literature review

description: Congenital hypogonadotropic hypogonadism (CHH) is a rare condition characterized by incomplete pubertal development, infertility, and gonadotropin-releasing hormone deficiency, associated with mutations in more than 50 genes. We aimed to conduct an etiological analysis of a CHH Chinese family and summarize the clinical presentations and genetic changes of reported similar cases. Whole-exome sequencing (WES) was performed to identify the molecular cause in the proband. In silico tools were employed to analyze the pathogenicity of the variants. Reported cases with similar clinical features and associated genes were summarized by searching through PubMed/MEDLINE using keywords ‘FGFR1,’ ‘CHH,’ and ‘Kallmann syndrome (KS).’ Genetic analysis revealed a novel likely pathogenic deletion mutation in the FGFR1 gene (NM_023110.3: c.263_264del (Val88Alafs*22)) in a Chinese family exhibiting micropenis and underdeveloped testes. A total of 38 cases with CHH or KS have been previously reported. This study identified a novel FGFR1 deletion variant responsible for CHH, expanding the known mutational spectrum of FGFR1. Typical manifestations include delayed puberty and diverse presentations. The genotype–phenotype correlation in CHH remains unclear and may involve oligogenic effects and epigenetic regulation.
DOI: 10.6084/m9.figshare.30479382
title: Global, regional, and national burden of polycystic ovary syndrome, 1990–2021: a comprehensive analysis of trends and projections based on the global burden of disease 2021 study

description: Polycystic ovarian syndrome (PCOS) is a major endocrine disorder that affects women of reproductive age. This study evaluated global disease burden trends (1990–2021) and projected future trajectories to 2050 to inform public health strategies. Using Global Burden of Disease 2021 data, we analyzed PCOS prevalence, incidence, and disability-adjusted life years (DALYs) and correlations with the sociodemographic index (SDI). Trends were assessed <i>via</i> the estimated annual percentage change, and future burden was projected using a Bayesian age-period-cohort model. From 1990 to 2021, global PCOS prevalence among reproductive - age women rose 89.55% to 69.47 million. Incident cases increased 55.90% to 2.30 million, and DALYs surged 87.70% to 607.76 thousand. Regions with rising SDI, particularly South, East, and Southeast Asia, saw the steepest increases in age-standardized rates. The incidence rose most sharply in the 10–19 age group, while the prevalence and DALYs peaked in the 15–49 age group. Projections indicate a continued increase in PCOS burden until 2050. PCOS poses a serious public health challenge, particularly in the medium-SDI regions. This escalating burden underscores the need for targeted interventions, particularly for adolescents and young women, to mitigate its long-term health impacts. Policymakers and clinicians must prioritize PCOS management to address its increasing global prevalence and associated disabilities.