Genome-Wide Linkage and Association Study of Childhood Gender Nonconformity in Males

Male sexual orientation is influenced by environmental and complex genetic factors. Childhood gender nonconformity (CGN) is one of the strongest correlates of homosexuality with substantial familiality. We studied brothers in families with two or more homosexual brothers (409 concordant sibling pairs in 384 families, as well as their heterosexual brothers), who self-recalled their CGN. To map loci for CGN, we conducted a genome-wide linkage scan (GWLS) using SNP genotypes. The strongest linkage peaks, each with significant or suggestive two-point LOD scores and multipoint LOD score support, were on chromosomes 5q31 (maximum two-point LOD = 4.45), 6q12 (maximum two-point LOD = 3.64), 7q33 (maximum two-point LOD = 3.09), and 8q24 (maximum two-point LOD = 3.67), with the latter not overlapping with previously reported strongest linkage region for male sexual orientation on pericentromeric chromosome 8. Family-based association analyses were used to identify associated variants in the linkage regions, with a cluster of SNPs (minimum association p = 1.3 × 10–8) found at the 5q31 linkage peak. Genome-wide, clusters of multiple SNPs in the 10–6 to 10–8p-value range were found at chromosomes 5p13, 5q31, 7q32, 8p22, and 10q23, highlighting glutamate-related genes. This is the first reported GWLS and genome-wide association study on CGN. Further increasing genetic knowledge about CGN and its relationships to male sexual orientation should help advance our understanding of the biology of these associated traits.

Low perinatal androgens predict recalled childhood gender nonconformity in men

The contributions of gender socialization and direct hormonal action on the brain in the development of human behavioral sex differences are subjects of intense scientific and social interest. Prior research indicates masculinized behavioral patterns in individuals with high prenatal androgen exposure raised as girls, but complementary evidence regarding individuals with low prenatal androgens raised as boys is critically lacking. We investigated recalled childhood gender nonconformity (CGN) in men (n = 65) and women (n = 32) with isolated GnRH deficiency (IGD) and typically developing men (n = 463) and women (n = 1207). IGD is characterized by low or absent gonadal hormone production after the first trimester of gestation until hormone replacement therapy initiation around the time of puberty, but external appearance is concordant with chromosomal and gonadal sex. Compared to typically developing men, men with IGD reported higher CGN, particularly if they also reported cryptorchidism at birth, a marker of low perinatal androgens. Women with IGD did not differ from typically developing women. These results suggest that early androgen exposure after the first trimester contributes to male-typical gender role behaviors in childhood.

“Our World Has Been Rocked”

This chapter turns to the area of gender and sexuality, and examines parents’ contrasts between “just gay” and “truly trans” explanations for childhood gender nonconformity. Given age-old statistics that link childhood gender nonconformity with adult homosexuality, these deliberations are no small part of parents’ journeys. Modern-day LGBT rights discourses assert a firm distinction between “gender” and “sexuality”—gender identity is one thing, sexual orientation is another. However, parents’ deliberations signaled something more fluid and potentially permeable between these two realms of self, across a morphing “spectrum” of possibilities. This conceptual work, the chapter argues, gives increasing intelligibility to (trans)gendered understandings, versus ones formerly understood within a grid of (homo)sexuality. In social-constructionist terms, this is not merely descriptive labor, but productive labor, helping to bring broadening transgender possibilities into being. This work also prioritizes child-rooted shifts in a way that further troubles firm distinctions between these categories of the self.