Western studies have consistently found that androphilic (sexually attracted to men) male-to-female transsexuals have a later birth order and a relative excess of brothers compared with appropriate control participants. However, non-Western studies on birth order and sibling sex ratio in androphilic males (transsexual or non-transsexual) are rare. The objective of the study was to test the hypothesis that androphilic male-to-female transsexuals have a late birth order and a relative excess of brothers in a non-Western culture with a higher fertility rate. The participants were 60 androphilic male-to-female transsexuals and 61 male heterosexual controls. The transsexual participants had significantly more older brothers than the control participants, but the groups did not differ in their numbers of older sisters, younger brothers, or younger sisters. The foregoing pattern is usually referred to as the “fraternal birth order effect.” Slater’s and Berglin’s Indexes both showed that the mean birth order of the control participants was very close to that expected from a random sample drawn from a demographically stable population whereas the mean birth order of the transsexual participants was later. A measure of sibship composition, brothers/all siblings, showed that the transsexual group had a higher proportion of male siblings compared with the control group. In conclusion, the present study found that Turkish androphilic male-to-female transsexuals show the same high fraternal birth order that has been found in comparable androphilic samples in Western Europe, North America, and the South Pacific, which suggests a common underlying biological causal mechanism.

Author/-s:       Ali Bozkurt; Ozlem Hekim Bozkurt; Ipek Sonmez

Publication:     Archives of Sexual Behavior, 2014

Web link:          http://link.springer.com/article/10.1007/s10508-014-0425-9

Introduction: The full etiology of transsexualism is still unknown. However many factors, like biological and environmental, are being suggested as possible explanations to the cause of this entity.

We intend to revisit the major etiological theories of transsexuality, based on the description of two cases occurring in first-degree relatives.

Case Reports: A mother and her daughter both diagnosed with Gender Identity Disorder are followed at Multidisciplinary Clinical Sexology Group in our facilities since 2011.

This case is related to a young girl who in her childhood felt and behaved himself as a boy by adopting male gender stereotypes. She has lived with distress during the development of female secondary sexual characteristics, and the age of 17, after identifying his problem decided to tell his mother. However our patient founded that her mother, with 38 years old, was already resigned by living with a sex gender that didn't recognize as her own. In the end they decided to confront the social and family environment, joining both in the process of sexual reassignment.

Conclusions: The transsexualism is a complex phenomenon. The occurrence of two cases of transsexualism in a mother and daughter highlights the importance of consider and extend the knowledge about the biological aspects of gender identity disorder.

It is relevant to communicate the cases occurring within the same family to contribute to the etiology investigation in this area. In the literature the rare cases described of family transsexuals are among brothers, which makes this case between mother and daughter special.

Author/-s:       I. Ferraz; T. Coelho; S. Silva; P. Rodrigues; J. Castedo; M. Mota

Publication:     European Psychiatry, 2014

Web link:          http://www.europsy-journal.com/article/S0924-9338(14)77901-5/abstract

The relative contributions of genetic and environmental factors to the development of gender identity have been debated. Twins were studied that are concordant or discordant for gender identity status in order to provide clarification of this issue. An extensive library search yielded reports of 27 male and 16 female sets concordant or discordant for transsexuality. An Internet bulletin board search and clinical contact requests for participants in a survey of twins in which one or both transitioned located 69 new twin pairs. In addition to asking about matters associated with gender, these new twins were asked about their transition, rearing, and sexual practices. Combining data from the present survey with those from past-published reports, 20 % of all male and female monozygotic twin pairs were found concordant for transsexual identity. This was more frequently the case for males (33 %) than for females (23 %). The responses of our twins relative to their rearing, along with our findings regarding some of their experiences during childhood and adolescence show their identity was much more influenced by their genetics than their rearing.

Author/-s:       Milton Diamond

Publication:     International Journal of Transgenderism, 2013

Web link:          http://www.tandfonline.com/doi/abs/10.1080/15532739.2013.750222#preview

Introduction: The etiology of gender identity disorder (GID) remains largely unknown. In recent literature, increased attention has been attributed to possible biological factors in addition to psychological variables.

Aim: To review the current literature on case studies of twins concordant or discordant for GID.

Methods: A systematic, comprehensive literature review.

Results: Of 23 monozygotic female and male twins, nine (39.1 %) were concordant for GID; in contrast, none of the 21 same-sex dizygotic female and male twins were concordant for GID, a statistically significant difference (P = 0.005). Of the seven opposite-sex twins, all were discordant for GID.

Conclusions: These findings suggest a role for genetic factors in the development of GID.

Author/-s:       Gunter Heylens; Griet de Cuypere; Kenneth J. Zucker; Cleo Schelfaut; Els Elaut; Heidi Vanden Bossche; Elfride de Baere; Guy T’Sjoen

Publication:     The Journal of Sexual Medicine, 2012

Web link:          http://onlinelibrary.wiley.com/doi/10.1111/j.1743-6109.2011.02567.x/abstract

Several sibship-related variables have been studied extensively in sexual orientation research, especially in men. Sibling sex ratio refers to the ratio of brothers to sisters in the aggregate sibships of a group of probands. Birth order refers to the probands’ position (e.g., first-born, middle-born, last-born) within their sibships. Fraternal birth order refers to their position among male siblings only. Such research was extended in this study to a large group of early-onset gender dysphoric adolescents. The probands comprised 94 male-to-female and 95 female-to-male gender dysphoric adolescents. The overwhelming majority of these were homosexual or probably prehomosexual. The control group consisted of 875 boys and 914 girls from the TRAILS study. The sibling sex ratio of the gender dysphoric boys was very high (241 brothers per 100 sisters) compared with the expected ratio (106:100). The excess of brothers was more extreme among the probands’ older siblings (300:100) than among their younger siblings (195:100). Between-groups comparisons showed that the gender dysphoric boys had significantly more older brothers, and significantly fewer older sisters and younger sisters, than did the control boys. In contrast, the only notable finding for the female groups was that the gender dysphoric girls had significantly fewer total siblings than did the control girls. The results for the male probands were consistent with prior speculations that a high fraternal birth order (i.e., an excess of older brothers) is found in all homosexual male groups, but an elevated sibling sex ratio (usually caused by an additional, smaller excess of younger brothers) is characteristic of gender dysphoric homosexual males. The mechanisms underlying these phenomena remain unknown.

Author/-s:       Sebastian E. E. Schagen; Henriëtte A. Delemarre-van de Waal; Ray Blanchard; Peggy T. Cohen-Kettenis

Publication:     Archives of sexual behaviour, 2012

Web link:          http://link.springer.com/article/10.1007%2Fs10508-011-9777-6

The aim of this thesis is examine biological and psychosocial factors that contribute to the development of gender-variant or gender-typical identities. Blanchard’s autogynephilia theory (Blanchard, 1989b) suggests that these factors are different in birth-assigned males with different sexual orientations. Previous research has found that genetics, prenatal hormone exposure, neuroanatomy, handedness, dermatoglyphics, fraternal birth order, and abuse are related to gender identity. While a number of investigators have studied these variables individually, this is the first known study to have examined the inter-relationships of these variables in one sample and to include participants with a wide range of gender identities. Data were collected from a convenience sample of 2 277 online-recruited participants with gender-variant and gender-typical identities using an online questionnaire. Participants were mainly white/Caucasian (92 %) adults living in the USA (54 %) and New Zealand (19 %). From the results, reported family concordance for gender-variance and a systematic review of case reports of twins with gender-variant identities indicated genetic determinants of gender identities. Finger-length ratio, systemising, and a systematic review of case reports of gender identity outcomes for adults with intersex and related conditions indicated prenatal hormone determinants of gender identities. Further evidence for biological factors came from elevated levels of non-right handedness among birth assigned females with gender-variant identities. Structural equation modelling showed that the positive relationship between abuse experience and degree of adult gender variance was partially mediated by recalled childhood gender-variance. This suggests abuse may be a cause as well as a result of gender-variance. Contrary to Blanchard’s theory, there were no differences in biological and psychosocial factors between birth-assigned male participants of different sexual orientations. This was the first research to find evidence that biological and psychosocial factors are the same for transsexuals as for persons with other gender-variant identities. Overall, these findings add support for a biological predisposition for gender-variant and gender-typical identities. Psychosocial determinants are likely to be complex and work in interaction with biological factors.

Author/-s:       Jaimie F. Veale

Publication:     Doctoral thesis, Massey University, Albany, New Zealand, 2011

Web link:          http://www.jaimieveale.com/wp-content/uploads/2012/09/PhD-thesis.pdf

This article reviews research on biological and psychosocial factors relevant to the etiology of gender-variant identities. There is evidence for a genetic component of gender-variant identities through studies of twins and other within-family concordance and through studies of specific genes. Evidence that prenatal androgens play a role comes from studies that have examined finger length ratios (2D:4D), prevalence of polycystic ovary syndrome among female-to-male transsexuals, and individuals with intersex and related conditions who are more likely to have reassigned genders. There is also evidence that transsexuals have parts of their brain structure that is typical of the opposite birth-assigned gender. A greater likelihood of non-right-handedness suggests developmental instability may also contribute as a biological factor. There is a greater tendency for persons with gender-variant identities to report childhood abuse and a poor or absent relationship with parents. It is unclear if this is a cause or effect of a gender-variant identity. Parental encouragement of gender-variance is more common among individuals who later develop a gender-variant identity. We conclude that biological factors, especially prenatal androgen levels, play a role in the development of a gender-variant identity and it is likely that psychosocial variables play a role in interaction with these factors.

Author/-s:       Jaimie F. Veale; David E. Clarke; Terri C. Lomax

Publication:     Personality and Individual Differences, 2010

Web link:          http://www.sciencedirect.com/science/article/pii/S0191886909004620

This study examined biological and psychosocial variables that are relevant to the etiology of gender-variance. Data were collected over the internet from 2277 participants of either gender who identified as transsexual, other gender-variant, and not gender-variant. We found number of gender-variant relatives, handedness, emotional abuse, finger length ratios (2D:4D), and systematizing significantly predicted Adult Gender-Variance among participants of both genders. Adult Gender-Variance was also predicted by number of older brothers among birth-assigned males. No significant differences were found in extreme right-handedness or mental rotation. No significant interaction effects were found with sexual orientation. While these findings are generally consistent with past research, there were limitations of the internet-based methodology, including a non-representative sample.

Author/-s:       Jaimie F. Veale; David E. Clarke; Terri C. Lomax

Publication:     Personality and Individual Differences, 2010

Web link:          http://www.sciencedirect.com/science/article/pii/S0191886910001790

Familial studies and reports of co-occurrence of gender identity disorder (GID) within a family may help to clarify the question of whether transsexualism is a familial phenomenon. In a sample of 995 consecutive transsexual probands (677 male-to-female [MF] and 318 female-to-male [FM]), we report 12 pairs of transsexual non-twin siblings (nine pairs of MF siblings, two pairs of MF-FM siblings, and one pair of FM siblings). The present study doubles the number of case reports of co-occurrence of transsexualism in non-twin siblings available in the literature. According to our data, the probability that a sibling of a transsexual will also be transsexual was 4.48 times higher for siblings of MF than for siblings of FM transsexual probands, and 3.88 times higher for the brothers than for the sisters of transsexual probands. Moreover, the prevalence of transsexualism in siblings of transsexuals (1/211 siblings) was much higher than the range expected according to the prevalence data of transsexualism in Spain. The study suggests that siblings of transsexuals may have a higher risk of being transsexual than the general population, and that the risk is higher for brothers than sisters of transsexuals, and for siblings of MF than FM transsexuals. Nevertheless, the risk is low.

Author/-s:       Esther Gómez-Gil; Isabel Esteva; M. Cruz Almaraz; Eduardo Pasaro; Santiago Segovia; Antonio Guillamon

Publication:     Archives of Sexual Behaviour, 2010

Web link:          http://link.springer.com/article/10.1007/s10508-009-9524-4

The sexual differentiation of the brain starts in the second semester of pregnancy, which is, after the development of the genitals which differentiate in the second month of pregnancy. Because these two processes have different timetables, it could be that these are initiated through different pathways. Male gonads synthesize testosterone, which can be converted into estrogen by aromatase in the brain. In humans, the exact mechanism of male and female brain development has still to be elucidated. Based on clinical evidence from genetic men (XY) suffering from a mutation in the androgen receptor gene (complete androgen-insensitivity syndrome) and who show a female phenotype of the external genitals as well as the brain, it can be proposed that direct action of testosterone is probably causing the brain to differentiate in the male direction. However, when the process of genital development and of brain sexual development does not match the same sex, females with a male brain and vice versa can arise. These transsexual people have problems with their gender identity and have the conviction of being born in the wrong body. Twin and family studies show that there are genetic factors influencing the chances of a gender identity problem. Genetic factors could play a large role in the sexual differentiation of the brain, as can be shown from studies where differential genetic expression is found before development of the gonads. These genes could also function in other tissues than gonads and influence the sexual differentiation of the brain. The DMRT gene family which encodes transcription factors or the amount of sex hormone binding globulin (SHBG) is possibly influencing the development of sex differences, just as sex-biased differential splicing. Epigenetic mechanisms such as X-inactivation and genomic imprinting are also good candidates for causing differences in the sexual differentiation of the brain. These observations indicate that probably many processes operate together in the sexual differentiation of the brain and that diverse mutations can lead to gender identity problems.

Author/-s:       L. A. Worrell

Publication:     Master Thesis, Faculty of Medicine, Universiteit Utrecht, 2010

Web link:          http://dspace.library.uu.nl/handle/1874/182733

The aim of this study was to investigate the prevalence of cross-gender behavior during childhood, to estimate the influence of genotype and environment on variation in cross-gender behavior, and to explore the association of cross-gender behavior with maternal ratings of behaviour problems as indexed by the Internalizing and Externalizing scales of the Child Behavior Checklist (CBCL). Crossgender behavior was assessed by two items from the CBCL: “behaves like opposite sex” and “wishes to be of opposite sex.” As part of an ongoing longitudinal study of the Netherlands Twin Registry, mothers were asked to complete the CBCL for their twins when they were 7 (n ≈ 14 000 twins) and 10 years old (n ≈ 8 500 twins). The prevalence of crossgender behavior (as measured by maternal report of behaving like or wishing to be the opposite sex) was 3.2 % and 5.2 % for 7-year-old boys and girls, respectively, and decreased to 2.4 % and 3.3 % for 10-year-old boys and girls. Surprisingly, the prevalence rate of cross-gender behavior of girls with a male co-twin was lower than of girls with a female co-twin. At both ages, the similarity for cross-gender behavior was greater in monozygotic than in dizygotic twins pairs. Genetic structural equation modeling showed that 70 % of the variance in the liability of cross-gender behavior could be explained by genetic factors, at both ages and for both sexes. Cross-gender behavior was associated with higher scores on Internalizing and Externalizing problems, both in boys and in girls.

Author/-s:       C. E. M. van Beijsterveldt; James J. Hudziak; Dorret I. Boomsma

Publication:     Archives of Sexual Behavior, 2006

Web link:          http://europepmc.org/abstract/MED/17109235

The genetic and environmental etiologies of sex-typed behavior were examined during the preschool years in a sample of 3 990 three- to four-year-old twin and non-twin sibling pairs. Results showed moderate genetic and significant shared environmental influence for boys and substantial genetic and moderate shared environmental influence for girls. For both boys and girls, twin-specific shared environmental effects contributed to twins’ similarity in gender role behavior and accounted for approximately 22 % of the shared environmentatal variance. These findings extend previous research conducted with older samples by showing not only important genetic contributions to gender role behavior but also an important role for shared environment. The inclusion of non-twin siblings showed that some of the shared environmental influence is specific to twins.

Author/-s:       Alessandra C. Iervolino; Melissa Hines; S. E. Golombok; J. Rust; Robert Plomin

Publication:     Child Development, 2005

Web link:          http://www.ncbi.nlm.nih.gov/pubmed/16026499

In this genetic study of atypical gender role development, parents of 5 799 twin pairs, ages 3 and 4, rated their twin children's masculinity and femininity. Boys were selected as gender atypical if they were highly feminine (top 5 %, 10 %, or 15 %) relative to other boys, and girls were selected if they were highly masculine relative to other girls. Gender-atypical boys and girls were each divided into 2 groups: fully gender atypical (e.g., feminine boys also low on masculinity) and partially gender atypical (e.g., feminine boys who are not low on masculinity). DeFries-Fulker (DF; J. C. DeFries & D. W. Fulker, 1985, 1988) extremes analysis yielded moderate group heritability and substantial shared environment effects for atypical gender role behavior. However, for fully gender-atypical girls, group heritability accounted for most of the variance, and shared environment had no effect. The results are discussed in light of past studies and potential implications for atypical gender development.

Author/-s:       Ariel Knafo; Alessandra C. Iervolino; Robert Plomin

Publication:     Journal of Personality and Social Psychology, 2005

Web link:          http://europepmc.org/abstract/MED/15841866

In previous research, a late birth order has been shown to be a characteristic of Western homosexual transsexual men. To date, however, it is not clear if a late birth order is specific to Western transsexuals or may be a characteristic of non-Western transgendered males as well. We quantified birth order in a sample of 13 transgendered males known as fa'afāfine from Samoa. On average, the fa'afāfine were late born, both with regard to number of older brothers and number of older sisters, although the effect appeared to be somewhat stronger with regard to number of older brothers. We consider possible interpretations of the late birth order effect, along with recommendations for further research to identify common mechanisms that might underlie transgenderism across different cultural groups.

Author/-s:       Kris H. Poasa; Ray Blanchard; Kenneth J. Zucker

Publication:     Journal of Sex amd Marital Therapy, 2004

Web link:          http://www.ncbi.nlm.nih.gov/pubmed/14660290

The heritability and prevalence of the gender identity disorder (GID) was examined, as well as its comorbidity with separation anxiety and depression, in a nonretrospective study of child and adolescent twins. The parents of 314 twins (ages 4–17 years; 96 monozygotic pairs [MZ] and 61 dizygotic [DZ] pairs) completed the Coolidge Personality and Neuropsychological Inventory (CPNI) containing a six-item DSM-IV-based GID scale. Prevalence of clinically significant GID symptomatology in the twin sample was estimated to be 2.3 %. Univariate model fitting analyses were conducted using an ordinal transformation of the GID scale. The model that best described the data included a significant additive genetic component accounting for 62 % of the variance and a nonshared environmental component accounting for the remaining 38 % of the variance. Results suggested no heterogeneity in the parameter estimates resulting from age. The correlation between GID and depression was modest, but significant (r = 0.20; P < 0.05), whereas the correlation between GID and separation anxiety was nonsignificant (P > 0.05). Overall, the results support the hypothesis that there is a strong heritable component to GID. The findings may also imply that gender identity may be much less a matter of choice and much more a matter of biology.

Author/-s:       Frederick L. Coolidge; Linda L. Thede; Susan E. Young

Publication:     Behavior genetics, 2002

Web link:          http://link.springer.com/article/10.1023%2FA%3A1019724712983

The authors recruited twins systematically from the Australian Twin Registry and assessed their sexual orientation and 2 related traits: childhood gender nonconformity and continuous gender identity. Men and women differed in their distributions of sexual orientation, with women more likely to have slight-to-moderate degrees of homosexual attraction, and men more likely to have high degrees of homosexual attraction. Twin concordances for nonheterosexual orientation were lower than in prior studies. Univariate analyses showed that familial factors were important for all traits, but were less successful in distinguishing genetic from shared environmental influences. Only childhood gender nonconformity was significantly heritable for both men and women. Multivariate analyses suggested that the causal architecture differed between men and women, and, for women, provided significant evidence for the importance of genetic factors to the traits’ covariation.

Author/-s:       J. Michael Bailey; Michael P. Dunne; Nicholas G. Martin

Publication:     Journal of Personality and Social Psychology, 2000

Web link:          http://psycnet.apa.org/?&fa=main.doiLanding&doi=10.1037/0022-3514.78.3.524

A significant skewing in the sex ratio in favour of females has been reported for the families of homosexual men such that there are fewer maternal uncles than aunts. This finding is repeated for a large series of transsexual families in this study. Four hundred and seventeen male-to-female transsexuals and 96 female-to-male transsexuals were assessed. Male-to-female transsexuals have a significant excess of maternal aunts vs. uncles. No differences from the expected parity were found for female-to-male transsexuals or on the paternal side. A posited explanation for these findings invokes X inactivation and genes on the X chromosome that escape inactivation but may be imprinted. Our hypothesis incorporates the known familial traits in the families of homosexuals and transsexuals by way of retention of the grand parental epigenotype on the X chromosome. Generation one would be characterized by a failure to erase the paternal imprints on the paternal X chromosome. Daughters of this second generation would produce sons that are XpY and XmY. Since XpY expresses Xist, the X chromosome is silenced and half of the sons are lost at the earliest stages of pregnancy because of the normal requirement for paternal X expression in extra-embryonic tissues. Females survive by virtue of inheriting two X chromosomes, and therefore the possibility of X chromosome counting and choice during embryonic development. In generation three, sons inheriting the paternal X after its second passage through the female germline survive, but half would inherit the feminizing Xp imprinted genes. These genes could pre-dispose the sons to feminization and subsequent development of either homosexuality or transsexualism.

Author/-s:       Richard Green; E. B. Keverne

Publication:     Journal of Theoretical Biology, 2000

Web link:         http://www.sciencedirect.com/science/article/pii/S0022519399910391

This study examined the birth order of girls with gender identity disorder (N=22). Each proband was matched to 3–7 clinical control girls for age at assessment and number of siblings (the mode number of controls per proband was 7) (total N=147). The number of older brothers, older sisters, younger brothers, and younger sisters was recorded. Slater’s birth order index showed that the probands were significantly more likely to be early born than were the controls. A modified Slater’s index also compared the birth order of the probands and the controls only to their brothers (when they had one or more) and only to their sisters (when they had one or more). Compared to the controls, the probands were born early compared to their sisters, but not to their brothers. These findings are the inverse of two previous studies of boys with gender identity disorder, who were later born relative to clinical control boys (11), an effect that appeared to be accounted for primarily by being born later relative to older brothers, but not to older sisters (46).

Author/-s:       Kenneth J. Zucker; S. Lightbody; K. Pecore; S. J. Bradley; Ray Blanchard

Publication:     European Child & Adolescent Psychiatry, 1998

Web link:          http://link.springer.com/article/10.1007/s007870050042

Sibling sex ratio (the ratio of brothers to sisters) was calculated for 444 boys with gender identity disorder (or with behaviors consistent with this diagnosis). The probands were ascertained from several researchers with expertise with this disorder and from the English language case report literature between 1938 and 1995. Among the probands with at least one sibling (N = 333), the results showed that boys with gender identity disorder had a significant excess of brothers to sisters, 131.1:100, when compared with the expected secondary sex ratio of 106:100. The excess of brothers replicated a previous study by Blanchard, Zucker, Bradley, and Hume (1995), in which the sibling sex ratio was 140.6:100. Further analyses showed that the probands were born later relative to their brothers than they were relative to their sisters. These findings are amenable to several psychosocial and biological explanations, which require further investigation.

Author/-s:       Kenneth J. Zucker; R. Green; S. Coates; B. Zuger; Peggy T. Cohen-Kettenis; G. M. Zecca; V. Lertora; J. Money; S. Hahn-Burke; S. J. Bradley; Ray Blanchard

Publication:     Journal of Child Psychology and Psychiatry, and Allied Disciplines, 1997

Web link:          http://europepmc.org/abstract/MED/9255698