Epigenetics is implicated in the basis of gender incongruence. An epigenome-wide association analysis.
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PROVIDER: PRJNA725309 | ENA |
REPOSITORIES: ENA
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Project description:The main objective was to carry out a global DNA methylation analysis in a population with gender incongruence before gender-affirming hormone treatment (GAHT), in comparison to a cisgender population.
2021-04-27 | GSE173382 | GEO
Project description:IntroductionThe main objective was to carry out a global DNA methylation analysis in a population with gender incongruence before gender-affirming hormone treatment (GAHT), in comparison to a cisgender population.MethodsA global CpG (cytosine-phosphate-guanine) methylation analysis was performed on blood from 16 transgender people before GAHT vs. 16 cisgender people using the Illumina© Infinium Human Methylation 850k BeadChip, after bisulfite conversion. Changes in the DNA methylome in cisgender vs. transgender populations were analyzed with the Partek® Genomics Suite program by a 2-way ANOVA test comparing populations by group and their sex assigned at birth.ResultsThe principal components analysis (PCA) showed that both populations (cis and trans) differ in the degree of global CpG methylation prior to GAHT. The 2-way ANOVA test showed 71,515 CpGs that passed the criterion FDR p < 0.05. Subsequently, in male assigned at birth population we found 87 CpGs that passed both criteria (FDR p < 0.05; fold change ≥ ± 2) of which 22 were located in islands. The most significant CpGs were related to genes: WDR45B, SLC6A20, NHLH1, PLEKHA5, UBALD1, SLC37A1, ARL6IP1, GRASP, and NCOA6. Regarding the female assigned at birth populations, we found 2 CpGs that passed both criteria (FDR p < 0.05; fold change ≥ ± 2), but none were located in islands. One of these CpGs, related to the MPPED2 gene, is shared by both, trans men and trans women. The enrichment analysis showed that these genes are involved in functions such as negative regulation of gene expression (GO:0010629), central nervous system development (GO:0007417), brain development (GO:0007420), ribonucleotide binding (GO:0032553), and RNA binding (GO:0003723), among others.Strengths and limitationsIt is the first time that a global CpG methylation analysis has been carried out in a population with gender incongruence before GAHT. A prospective study before/during GAHT would provide a better understanding of the influence of epigenetics in this process.ConclusionThe main finding of this study is that the cis and trans populations have different global CpG methylation profiles prior to GAHT. Therefore, our results suggest that epigenetics may be involved in the etiology of gender incongruence.
| S-EPMC8418298 | biostudies-literature
Project description:Sexual reproduction is a complex process involving multiple pathways. In this study, we aimed at investigating gene expression profiles underlying gender specificity in the zebrafish. To do so, we analyzed the transcriptome of the gonads of breeding fish and queried the gene expression profiles for significant differences between the genders and also between stages of gonad development. Major differences in gene expression profiles between genders were encountered at the level of the gonads. In addition, we identified biological processes associated with stage of sexual development in female gonads. Keywords: gender and stage related gene expression
2007-03-22 | GSE6063 | GEO
Project description:Analysis of Foxp3(+)epigenetics(-) T cells, Foxp3(-)epigenetics(+) T cells, and Foxp3(+)epigenetics(+) T cells. Results indicate regulatory T cell (Treg) ontogenesis requires two independent processes, expression of the transcription factor Foxp3 and establishment of Treg epigenetic programs induced by T cell receptor (TCR) stimulation.
2012-11-05 | GSE25252 | GEO
Project description:Incongruence between transcriptional and vascular pathophysiological cell states
| PRJNA967005 | ENA
Project description:The role of environmental factors and gender disparities as determinants of health is incontrovertible. In the digestive sphere, it is noteworthy that one of the most prevalent diseases such as irritable bowel syndrome (IBS) has a predominance in females. The origin of IBS is related to mucosal microinflammation phenomena, psychosocial stress, and in the last years, alterations in gut microbiota. Recent observations from our group in healthy subjects, demonstrate that both chronic psychosocial stress, and female gender per se determine a significant intestinal epithelial barrier dysfunction in response to intercurrent stimuli, which, in susceptible individuals, could result in an early stage in the development of more lasting changes and the onset of clinical manifestations of IBS. Although the intimate mechanisms involved in stress-induced intestinal pathophysiology are not well known, diverse studies suggest that gut microbiota alteration, through epigenetic modifications of the main stress-mediators could be one of them. However, solid scientific evidence demonstrating the influence of stress on gut microbiota and epigenetics of the main stress-mediators is missing. Therefore, we want to investigate and characterize gender-dependent epigenetic modifications involved in intestinal barrier dysfunction in response to acute stress. The identification of gender-dependent abnormal epigenetic patterns related to female gender dysfunction can make a breakthrough in the understanding of the pathophysiology of the regulation of intestinal permeability, and promote positive diagnostic and therapeutic future progress in IBS.
2024-02-15 | E-MTAB-10158 | biostudies-arrayexpress
Project description:IntroductionBrain sexual differentiation results from the effects of sex steroids on the developing brain. The presumptive route for brain masculinization is the direct induction of gene expression via activation of the estrogen receptors α and β and the androgen receptor through their binding to ligands and to coactivators, regulating the transcription of multiple genes in a cascade effect.AimTo analyze the implication of the estrogen receptor coactivators SRC-1, SRC-2, and SRC-3 in the genetic basis of gender incongruence.Main outcome measuresAnalysis of 157 polymorphisms located at the estrogen receptor coactivators SRC-1, SRC-2, and SRC-3, in 94 transgender versus 94 cisgender individuals.MethodUsing SNPStats software, the allele and genotype frequencies were analyzed by χ2, the strength of the association was measured by binary logistic regression, estimating the odds ratio for each genotype. Measurements of linkage disequilibrium and haplotype frequencies were also performed.ResultsWe found significant differences at level P < .05 in 8 polymorphisms that correspond to 5.09% of the total. Three were located in SRC-1 and 5 in SRC-2. The odds ratio analysis showed significant differences at level P < .05 for multiple patterns of inheritance. The polymorphisms analyzed were in linkage disequilibrium. The SRC-1 haplotypes CGA and CGG (global haplotype association P < .009) and the SRC-2 haplotypes GGTAA and GGTAG (global haplotype association P < .005) were overrepresented in the transgender population.ConclusionThe coactivators SRC-1 and SRC-2 could be considered as candidates for increasing the list of potential genes for gender incongruence. Ramírez KDV, Fernández R, Delgado-Zayas E, et al. Implications of the Estrogen Receptor Coactivators SRC1 and SRC2 in the Biological Basis of Gender Incongruence. Sex Med 2021;9:100368.
| S-EPMC8240342 | biostudies-literature
Project description:Analysis of Foxp3(+)epigenetics(-) T cells, Foxp3(-)epigenetics(+) T cells, and Foxp3(+)epigenetics(+) T cells. Results indicate regulatory T cell (Treg) ontogenesis requires two independent processes, expression of the transcription factor Foxp3 and establishment of Treg epigenetic programs induced by T cell receptor (TCR) stimulation. GFP+CD4+ and GFP-CD4+ splenocytes were sorted from DEREG and DEREG/Scurfy mice. These cells were activated with anti-CD3/CD28 antibodies, and then transduced with Foxp3-expressing retrovirus (pGCSamIN, NGFR marker). NGFR+ T cells sorted were subjected to microarray analysis (Affymetrix, mouse genome 430 2.0 array). To normalize the experimental conditions, Tregs (GFP+ T cells from DEREG) and Tconv (GFP- T cells from DEREG) were also activated and transduced with empty vector. Two replicates each.
2012-11-05 | E-GEOD-25252 | biostudies-arrayexpress
Project description:During adolescence, many individuals with gender incongruence (GI) experience distress related to body dissatisfaction. This study aims to describe the body (dis)satisfaction of Dutch adolescents referred for GI and to describe the influence of body image on their psychological functioning. Self-report measures on body satisfaction (Body Image Scale) and psychological functioning (Youth Self-Report) were obtained from 787 adolescents (aged 10-18) who were referred to the Center of Expertise on Gender Dysphoria at the Amsterdam University Medical Centers between 1996 and 2016. First, a general description of body satisfaction in adolescents with GI was developed. Secondly, multiple linear regression analyses were performed to determine the association between body image and psychological functioning, both for total problems and for internalizing and externalizing problems separately. Third, regression analyses are repeated for body area subscales. Adolescents with GI report the greatest dissatisfaction with the genital area, regardless of birth-assigned sex. For all other body areas, there were birth-assigned sex differences in satisfaction. The analyses showed that body satisfaction was significantly related to total psychological problems and both internalizing and externalizing problems. Greater body dissatisfaction is significantly associated with worse psychological functioning in adolescents with GI. Clinicians should monitor the body image of adolescents with GI over time, especially during puberty and medical interventions.
| S-EPMC9963492 | biostudies-literature