Born This Way: Using Intrinsic Disorder to Map the Connections between SLITRKs, TSHR, and Male Sexual Orientation

Basavanhally, Tara; Fonseca, Renee; Uversky, Vladimir N.

doi:10.1002/pmic.201800307

Cited by 4 publications

(5 citation statements)

References 167 publications

(187 reference statements)

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“…Some genetic loci , either X-linked or autosomal, have been reported - even though inconsistently and with a varying degree of replicability and reproducibility—to be associated with some human sexuality-related phenotypes and traits ( Rodríguez-Larralde and Paradisi, 2009 ; Basavanhally et al, 2018 ; Chiang and Park, 2020 ). Autosomal loci have been explained by formulating various hypotheses, including overdominance, conferring male heterozygote advantages, whilst the “sexually antagonistic selection” theory ( Camperio Ciani et al, 2015 ) could clarify the apparent paradox of X-linked loci , the molecular mechanisms through which persist and are transmitted “against all odds” of the evolutionary pressure.…”

Section: Discussionmentioning

confidence: 99%

Probing the genomic landscape of human sexuality: a critical systematic review of the literature

Bragazzi,

Converti,

Crapanzano

et al. 2023

Front. Genet.

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Whether human sexuality is the result of nature or nurture (or their complex interplay) represents a hot, often ideologically driven, and highly polarized debate with political and social ramifications, and with varying, conflicting findings reported in the literature. A number of heritability and behavioral genetics studies, including pedigree-based investigations, have hypothesized inheritance patterns of human sexual behaviors. On the other hand, in most twin, adoption, and nuclear family studies, it was not possible to disentangle between underlying genetic and shared environmental sources. Furthermore, these studies were not able to estimate the precise extent of genetic loading and to shed light both on the number and nature of the putative inherited factors, which remained largely unknown. Molecular genetic studies offer an unprecedented opportunity to overcome these drawbacks, by dissecting the molecular basis of human sexuality and allowing a better understanding of its biological roots if any. However, there exists no systematic review of the molecular genetics of human sexuality. Therefore, we undertook this critical systematic review and appraisal of the literature, with the ambitious aims of filling in these gaps of knowledge, especially from the methodological standpoint, and providing guidance to future studies. Sixteen studies were finally retained and overviewed in the present systematic review study. Seven studies were linkage studies, four studies utilized the candidate gene approach, and five studies were GWAS investigations. Limitations of these studies and implications for further research are discussed.

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Section: Discussionmentioning

confidence: 99%

Probing the genomic landscape of human sexuality: a critical systematic review of the literature

Bragazzi,

Converti,

Crapanzano

et al. 2023

Front. Genet.

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“…We selected 205 putative target genes that have been associated with gender incongruence, nonheterosexual orientation, disorders of sex development, sex hormone biosynthesis, the hypothalamus-pituitary-gonadal axis, regulation of puberty, sex-specific expression in the brain, or the 2D:4D digit ratio. 16 , 19 , 20 , 28 –52 The 2D:4D digit ratio was reported as a marker for prenatal androgen exposure. 50 We designed a custom target enrichment panel (HaloPlex HS; Agilent Technologies) with SureDesign (Agilent Technologies) to construct DNA libraries.…”

Section: Methodsmentioning

confidence: 99%

“… 18 Moreover, genome-wide association studies identified various genomic loci correlated with same-gender sexual orientation. 19 , 20 …”

Section: Introductionmentioning

confidence: 99%

Variations in gender identity and sexual orientation of university students

Yoshida,

Matsubara,

Ogata-Kawata

et al. 2023

Sexual Medicine

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Background Previous studies have shown that a small percentage of people in the general population have atypical gender identity and/or sexual orientation. Aim This study aimed to explore variations in gender identity and sexual orientation in university students and determine genetic factors associated with these variations. Methods Deviations from complete gender congruence and exclusive heterosexual orientation in 736 Japanese university students were quantitatively assessed with self-assessment questionnaires. Next, we conducted genetic tests for 80 participants who showed relatively low gender identity scores and/or atypical sexual orientation. These genetic tests consisted of repeat number analysis of the androgen receptor gene (AR) and a SKAT-O: an optimal unified sequence kernel association test, which is an exome-based rare variant association study. The results of the genetic tests were compared with the Japanese reference data and the results of our 637 control samples. Outcomes We calculated the gender identity and sexual orientation scores of all participants and analyzed the molecular data of 80 selected participants. Results The gender identity scores of 736 participants were broadly distributed: only ~15% of natal males and ~5% of natal females had the maximum score that corresponds to complete gender congruence. The sexual orientation scores also varied: ~80% of natal males and ~60% of natal females showed exclusive heterosexual orientation. We found no association between gender characteristics and AR repeat numbers. The SKAT-O showed that rare damaging variants of TDRP and 3 other genes were more common in the 80 participants than in the control group. Clinical Implications Our data support the view that gender is a phenotypic continuum rather than a binary trait. Strength and Limitations This study quantitatively assessed the gender characteristics of a large cohort of university students. Moreover, we conducted systematic screening for genetic factors associated with gender variations. The weaknesses of the study were the limited analytic power of the questionnaires, the relatively small sample for molecular analyses, and incomplete clinical information and relatively advanced ages of the control group. Conclusion This study revealed significant variations in gender identity and sexual orientation in university students, which may be partly associated with variants in TDRP or other genes.

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“…Single nucleotide polymorphism (SNP) in SLITRK-5, SLITRK-6, and Thyrotropin Receptor (TSHR) genes are some of the clinical factors that are associated with homosexuality in men [47,48]. There are also some associations between homosexuality in men and Grave's disease, which homosexual men are more likely to suffer from Grave's disease [49] and linked with the mutation in TSHR and deviation in the inactivation of X chromosome [48].…”

Section: The Clinical Sign Of Homosexual Menmentioning

confidence: 99%

Same Sexual Orientation as a Potential Risk Factor for Severe Mental Illness

2023

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Considered as a minority, the LGBTQ (Lesbian, Gay, Bisexual, Transgender, and Queer) community including homosexual males is more prone to mental distress. Studies on prevalence stated that sexual orientation minorities are susceptible to inept mental health outcomes, and the rate of anxiety disorders, schizophrenia, and psychotic illness is twice higher in gay and bisexual men rather than in heterosexuals. Along with that, several investigations found similarity between structural features in the brain of schizophrenic patients and homosexual males. This study intends to analyze the male homosexuality as a potential risk factor for schizophrenia. According to MRI (magnetic resonance imaging) findings, brain structures similarity is found between schizophrenic patients and homosexual men specifically on the thalamic grey matter volume and cortical thickness of the brain. Both schizophrenic patients and homosexual males exhibit reduced grey matter volume in the thalamus region, meanwhile schizophrenic patients have lower grey matter volume in the left putamen and homosexual males showed higher left putamen grey matter volume compared to heterosexual individuals. The cortex of schizophrenic patients is thinner in left orbitofrontal, right parahippocampal, and superior temporal area, resembling to thinner cortex in the right lateral orbitofrontal regions and regions in the visual cortex of homosexual males. Based on the reviewed journals, male homosexuality can be a potential risk factor for schizophrenia considering their correlation in neurodevelopmental deviations. Nevertheless, further investigations are needed regarding other factors and pathways causing such structural brain changes in both conditions. Keywords: grey matter, homosexual, neurodevelopmental, schizophrenia

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Born This Way: Using Intrinsic Disorder to Map the Connections between SLITRKs, TSHR, and Male Sexual Orientation

Cited by 4 publications

References 167 publications

Probing the genomic landscape of human sexuality: a critical systematic review of the literature

Probing the genomic landscape of human sexuality: a critical systematic review of the literature

Variations in gender identity and sexual orientation of university students

Same Sexual Orientation as a Potential Risk Factor for Severe Mental Illness

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