Project description:Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, Pmeta = 8.36 × 10-8, OR = 1.29; rs7259428, 19q12, ZNF536, Pmeta = 7.58 × 10-8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, Pmeta = 1.95 × 10-8; rs2414487, 15q21.3, LOC145783, Pmeta = 4.53 × 10-9; rs2106525, 7q31.1, MDFIC, Pmeta = 6.24 × 10-9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.
Project description:Family and twin studies suggest that genes play a role in male sexual orientation. We conducted a genome-wide association study (GWAS) of male sexual orientation on a primarily European ancestry sample of 1,077 homosexual men and 1,231 heterosexual men using Affymetrix single nucleotide polymorphism (SNP) arrays. We identified several SNPs with p?<?10-5, including regions of multiple supporting SNPs on chromosomes 13 (minimum p?=?7.5?×?10-7) and 14 (p?=?4.7?×?10-7). The genes nearest to these peaks have functions plausibly relevant to the development of sexual orientation. On chromosome 13, SLITRK6 is a neurodevelopmental gene mostly expressed in the diencephalon, which contains a region previously reported as differing in size in men by sexual orientation. On chromosome 14, TSHR genetic variants in intron 1 could conceivably help explain past findings relating familial atypical thyroid function and male homosexuality. Furthermore, skewed X chromosome inactivation has been found in the thyroid condition, Graves' disease, as well as in mothers of homosexual men. On pericentromeric chromosome 8 within our previously reported linkage peak, we found support (p?=?4.1?×?10-3) for a SNP association previously reported (rs77013977, p?=?7.1?×?10-8), with the combined analysis yielding p?=?6.7?×?10-9, i.e., a genome-wide significant association.
Project description:Several biological mechanisms have been proposed to influence male sexual orientation, but the extent to which these mechanisms cooccur is unclear. Putative markers of biological processes are often used to evaluate the biological basis of male sexual orientation, including fraternal birth order, handedness, and familiality of same-sex sexual orientation; these biomarkers are proxies for immunological, endocrine, and genetic mechanisms. Here, we used latent profile analysis (LPA) to assess whether these biomarkers cluster within the same individuals or are present in different subgroups of nonheterosexual men. LPA defined four profiles of men based on these biomarkers: 1) A subgroup who did not have these biomarkers, 2) fraternal birth order, 3) handedness, and 4) familiality. While the majority of both heterosexual and nonheterosexual men were grouped in the profile that did not have any biomarker, the three profiles associated with a biomarker were composed primarily of nonheterosexual men. We then evaluated whether these subgroups differed on measures of gender nonconformity and personality that reliably show male sexual orientation differences. The subgroup without biomarkers was the most gender-conforming whereas the fraternal birth order subgroup was the most female-typical and agreeable, compared with the other profiles. Together, these findings suggest there are multiple distinct biodevelopmental pathways influencing same-sex sexual orientation in men.
Project description:Previous neuroimaging studies demonstrated sex and also sexual orientation related structural and functional differences in the human brain. Genetic information and effects of sex hormones are assumed to contribute to the male/female differentiation of the brain, and similar effects could play a role in processes influencing human's sexual orientation. However, questions about the origin and development of a person's sexual orientation remain unanswered, and research on sexual orientation related neurobiological characteristics is still very limited. To contribute to a better understanding of the neurobiology of sexual orientation, we used magnetic resonance imaging (MRI) in order to compare regional cortical thickness (Cth) and subcortical volumes of homosexual men (hoM), heterosexual men (heM) and heterosexual women (heW). hoM (and heW) had thinner cortices primarily in visual areas and smaller thalamus volumes than heM, in which hoM and heW did not differ. Our results support previous studies, which suggest cerebral differences between hoM and heM in regions, where sex differences have been reported, which are frequently proposed to underlie biological mechanisms. Thus, our results contribute to a better understanding of the neurobiology of sexual orientation.
Project description:Male sexual orientation is a scientifically and socially important trait shown by family and twin studies to be influenced by environmental and complex genetic factors. Individual genome-wide linkage studies (GWLS) have been conducted, but not jointly analyzed. Two main datasets account for > 90% of the published GWLS concordant sibling pairs on the trait and are jointly analyzed here: MGSOSO (Molecular Genetic Study of Sexual Orientation; 409 concordant sibling pairs in 384 families, Sanders et al. (2015)) and Hamer (155 concordant sibling pairs in 145 families, Mustanski et al. (2005)). We conducted multipoint linkage analyses with Merlin on the datasets separately since they were genotyped differently, integrated genetic marker positions, and combined the resultant LOD (logarithm of the odds) scores at each 1 cM grid position. We continue to find the strongest linkage support at pericentromeric chromosome 8 and chromosome Xq28. We also incorporated the remaining published GWLS dataset (on 55 families) by using meta-analytic approaches on published summary statistics. The meta-analysis has maximized the positional information from GWLS of currently available family resources and can help prioritize findings from genome-wide association studies (GWAS) and other approaches. Although increasing evidence highlights genetic contributions to male sexual orientation, our current understanding of contributory loci is still limited, consistent with the complexity of the trait. Further increasing genetic knowledge about male sexual orientation, especially via large GWAS, should help advance our understanding of the biology of this important trait.
Project description:Pubic hair grooming is a common practice in the United States and coincides with prevalence of grooming-related injuries. Men who have sex with men (MSM) groom more frequently than men who have sex with women (MSW). We aim to characterize the influence of sexual orientation and sexual role on grooming behavior, injuries, and infections in men in the United States.We conducted a nationally representative survey of noninstitutionalized adults aged 18-65 residing in the United States. We examined the prevalence and risk factors of injuries and infections that occur as a result of personal grooming.Of the 4,062 men who completed the survey, 3,176 (78.2%) report having sex with only women (MSW), 198 (4.9%) report sex with men (MSM), and 688 (16.9%) report not being sexually active. MSM are more likely to groom (42.5% vs. 29.0%, P?<?0.001) and groom more around the anus, scrotum, and penile shaft compared with MSW. MSM receptive partners groom more often (50.9% vs. 26.9%, P?=?0.005) and groom more for sex (85.3% vs. 51.9%, P?<?0.001) compared with MSM insertive partners. MSM report more injuries to the anus (7.0% vs. 1.0%, P?<?0.001), more grooming-related infections (7.0% vs. 1.0%, P?<?0.001) and abscesses (8.8% vs. 2.5%, P?=?0.010), as well as lifetime sexually transmitted infections (STIs) (1.65 vs. 1.45, P?=?0.038) compared with MSW. More receptive partners report grooming at the time of their STI infection (52.2% vs. 14.3%, P?<?0.001) compared with insertive partners.Sexual orientation, and in particular sexual role, may influence male grooming behavior and impact grooming-related injuries and infections. Anogenital grooming may put one at risk for an STI. Healthcare providers should be aware of different grooming practices in order to better educate safe depilatory practices (i.e., the use of electric razors for anogenital grooming) in patients of all sexual orientations.