Rights are not decided by science but by law and laws are made by man. However, in this scientific age it has been decided that people who are members of a minority by nature generally have the same rights as anyone else. This is known as biological essentialism. Most transgender activist do not accept this, for the sake of discussion let us accept it. Therefore, the question of transgender rights comes down to how science answers the following questions.Do transgender people have the choice of completely conforming to gender norms and just being manly men or feminine women? Does the available data show that transgender people exist due to genetic, hormonal, neurological and or any other physical and immutable cause?Does hormone therapy for enough time or given early enough in life level the playing field for sports, and what variables effect this? What are the broader human rights implications of the answers to the above?Multiple independent studies have demonstrated a high probability that mutations to the Androgen Receptor (AR) and estrogen receptor genes ERβ \cite{Fernandez2018} \cite{2019NatSR...920099T}These genetic differences correspond to various differences in brain strucutre such that sexually dimorphic brain structures of transwomen match those of ciswomen, and those of transmen match those of cismen. \cite{Boucher}The differences are also mannifested in the form of reduced fertility and general undermasculinization even prior to any hormone treatment. \cite{Amir2022} The above finding is backed by MULTIPLE independent expert, peer reviewed, published meta analysis, a study of all available studies. \cite{DAndrea2020} Crucially for the issue of fairness in sports there are relevant endocrinological differences. \cite{endocsoc}A study done on post pubescent transgender adults by \cite{Hiltona} concluded a large advantage for transgender women in every sport, however, this article was corrected by the journal due to their undisclosed confict of interest. \cite{Hilton}A further study, also cited by Hilton as being well done, found after 1-2 years on hormones little to no difference in strength but a 5% advantage in speed for transwomen. \cite{Roberts577}Based on \cite{Roberts577} the British Journal of Sports Medicine concluded that given the data on competitors who are transitioning as young adults at the elite and collegiate levels there can be a difference that confers advantage, at the same time at the high school, youth and recreational levels when all the data is considered there is not necessarily an advantage. \cite{BJSM}Annotated Bibliography with Abstracts Findings based on Genetic research. Transgenderism is caused by mutations of the androgen and estrogen receiptor genes with effects on brain development, particularly in the basal ganglia. My Notes are in RED any emphasis is mine.Fernández, Rosa / Guillamon, Antonio / Cortés-Cortés, Joselyn / Gómez-Gil, Esther / Jácome, Amalia / Esteva, Isabel / Almaraz, MariCruz / Mora, Mireia / Aranda, Gloria / Pásaro, Eduardo Molecular basis of Gender Dysphoria: androgen and estrogen receptor interaction2018 Psychoneuroendocrinology , Vol. 98 p. 161-167 https://doi.org/10.1038/s41598-019-53500-y \cite{Fernandez2018} Abstract: Background: Polymorphisms in sex steroid receptors have been associated with transsexualism. However, published replication studies have yielded inconsistent findings, possibly because of a limited sample size and/or the heterogeneity of the transsexual population with respect to the onset of dysphoria and sexual orientation. We assessed the role of androgen receptor (AR), estrogen receptors alpha (ERα) and beta (ERβ), and aromatase (CYP19A1) in two large and homogeneous transsexual male-to-female (MtF) and female-to-male (FtM) populations.Methods: The association of each polymorphism with transsexualism was studied with a twofold subject-control analysis: in a homogeneous population of 549 early onset androphilic MtF transsexuals versus 728 male controls, and 425 gynephilic FtMs versus 599 female controls. Associations and interactions were investigated using binary logistic regression.Results: Our data show that specific allele and genotype combinations of ERβ, ERα and AR are implicated in the genetic basis of transsexualism, and that MtF gender development requires AR, which must be accompanied by ERβ . An inverse allele interaction between ERβ and AR is characteristic of the MtF population: when either of these polymorphisms is short, the other is long. ERβ and ERα are also associated with transsexualism in the FtM population although there was no interaction between the polymorphisms. Our data show that ERβ plays a key role in the typical brain differentiation of humans.Theisen, J. Graham / Sundaram, Viji / Filchak, Mary S. / Chorich, Lynn P. / Sullivan, Megan E. / Knight, James / Kim, Hyung-Goo / Layman, Lawrence C. The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants 2019-12 Nature Scientific Reports , Vol. 9 p. 20099 https://doi.org/10.1038/s41598-019-53500-y \cite{2019NatSR...920099T}Abstract: Approximately 0.5–1.4% of natal males and 0.2–0.3% of natal females meet DSM-5 criteria for gender dysphoria, with many of these individuals self-describing as transgender men or women. Despite recent improvements both in social acceptance of transgender individuals as well as access to gender affirming therapy, progress in both areas has been hampered by poor understanding of the etiology of gender dysphoria. Prior studies have suggested a genetic contribution to gender dysphoria, but previously proposed candidate genes have not yet been verified in follow-up investigation. In this study, we expand on the topic of gender identity genomics by identifying rare variants in genes associated with sexually dimorphic brain development and exploring how they could contribute to gender dysphoria. To accomplish this, we performed whole exome sequencing on the genomic DNA of 13 transgender males and 17 transgender females. Whole exome sequencing revealed 120,582 genetic variants. After filtering, 441 variants in 421 genes remained for further consideration, including 21 nonsense, 28 frameshift, 13 splice-region, and 225 missense variants. Of these, 21 variants in 19 genes were found to have associations with previously described estrogen receptor activated pathways of sexually dimorphic brain development. These variants were confirmed by Sanger Sequencing. Our findings suggest a new avenue for investigation of genes involved in estrogen signaling pathways related to sexually dimorphic brain development and their relationship to gender dysphoria.D’Andrea, Settimio / Pallotti, Francesco / Senofonte, Giulia / Castellini, Chiara / Paoli, Donatella / Lombardo, Francesco / Lenzi, Andrea / Francavilla, Sandro / Francavilla, Felice / Barbonetti, Arcangelo Polymorphic Cytosine-Adenine-Guanine Repeat Length of Androgen Receptor Gene and Gender Incongruence in Trans Women: A Systematic Review and Meta-Analysis of Case-Control Studies 2020 The Journal Of Sexual Medicine , Vol. 17 p. 543-550 https://doi.org/10.1016/j.jsxm.2019.12.010 \cite{DAndrea2020}Abstract: Introduction: It has been hypothesized that gender incongruence in transgender women could result from an antenatal impaired androgen activity on the developing brain. As the length of polymorphic cytosine-adenine-guanine (CAG) repeat sequences in the androgen receptor (AR) gene is inversely correlated with AR transcriptional activity, some studies explored a possible association between long CAG repeats and gender incongruence in trangender women. Yet results remain inconclusive. Aim: To systematically evaluate whether a difference exists in the length of AR CAG repeat sequences between trans women and men without gender incongruence.Methods: A thorough search of Medline, Scopus, Cochrane Library, Web of Science, and CINAHL databases was carried out to identify suitable case-control studies. Methodological quality of the included articles was assessed using the Newcastle-Ottawa Scale. In the absence of between-studies heterogeneity, as assessed by the Cochrane’s Q and I2 tests, standardized mean differences (SMDs) in the length of AR CAG repeats were combined using a fixed effect model. Funnel plot and trim-and-fill analysis were used to assess publication bias.Main outcome measure: The association of gender incongruence in transgender women with longer length of AR CAG repeat sequences was evaluated by calculating pooled standardized mean difference with 95% confidence interval (CI).Results: 5 studies included in the quantitative analysis collectively provided information on 795 trans women and 1,355 control men. At the overall estimate, the MtF group exhibited a significantly longer length of AR CAG repeat sequences (pooled standardized mean difference: 0.13, 95% CI: 0.04 to 0.22; P = 0.005; I2 = 0%, Pfor heterogeneity = 0.51). Sensitivity analysis demonstrated the high stability of the result. Funnel plot revealed a possible publication bias, and the trim-and-fill test detected 2 putative missing studies. Nevertheless, the significant association persisted even when pooled estimate was adjusted for publication bias.Clinical implications: These findings could suggest a contribution of a genetically mediated impairment in androgen signaling in development of gender incongruence for transgender women.Strength & limitations: This is the first meta-analysis exploring the relationship between AR CAG repeat polymorphism and gender incongruence. However, interactions with other functional genetic variants were not explored, and caution should be exercised when generalizing these results because of the possible variability in the distribution of CAG repeats among different populations and ethnic groups.Conclusion: Trans woman population exhibits significantly longer polymorphic CAG repeat sequences in the AR gene. Further studies are warranted to elucidate whether, how and to what extent multiple functional variants in sex hormone signaling genes could be associated with gender incongruence/dysphoria.Note: Every scientific study ever has said that further studies are needed for two basic reasons. One is that science is never totally done, though it can be settled beyond any scintilla of doubt, and since performing these studies is our job, we would always like to keep doing it!Boucher, Ferdinand J. O. / Chinnah, Tudor I. Gender Dysphoria: A Review Investigating the Relationship Between Genetic Influences and Brain Development 2020 Adolescent Health, Medicine and Therapeutics , Vol. Volume 11 p. 89-99 https://doi.org/10.2147/ahmt.s259168 \cite{Boucher}Abstract: Gender dysphoria (GD) is a facet of modern human biology which is believed to be derived from the sexual differentiation of the brain. GD “involves a conflict between a person’s physical or assigned gender and the gender with which he/she/they identify”, as defined in the DSM-5. Individuals report feeling uncomfortable and faced with prejudice from those around them, affecting their mental health. Elucidating the relationship between genetic influences on gonadal and brain development could give an insight into understanding this clinical condition. To explore this issue, a review of the literature database was carried out. Evidence suggests that abnormal biological processes, including mutations in certain genes, can lead to abnormal gonadal development, causing some fetuses to present with indifferent gonads and to be reassigned at birth to the default female sex. This disparity in genetic influences relates to an increased likelihood of a diagnosis of GD. An investigation into complete androgen insensitivity syndrome, involving androgen receptor (AR) gene mutation, suggests that such individuals also experience GD. It is known that the brains of males and females are different. Evidence further suggests that brain anatomy and neuronal signaling pathways are more closely aligned with a person’s perceived gender identity. Individuals who present with discordant gonadal and brain developments experience psychological challenges that may contribute to a state of unease or generalized dissatisfaction with their biological sex. These point to a possible biological and genetic underpinning of GD as stemming from a discordance between gonadal and brain development. However, not enough evidence has associated these differences with GD. Further research is required to elucidate the true mechanisms and possible inheritance pattern of GD for a better education and greater understanding by clinicians and the general public on perceptions regarding GD.