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

AbstractMale 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.

Download Full-text

Genome-Wide Linkage Study Meta-Analysis of Male Sexual Orientation

Archives of Sexual Behavior ◽

10.1007/s10508-021-02035-3 ◽

2021 ◽

Author(s):

Alan R. Sanders ◽

Gary W. Beecham ◽

Shengru Guo ◽

Judith A. Badner ◽

Sven Bocklandt ◽

...

Keyword(s):

Sexual Orientation ◽

Association Studies ◽

Meta Analysis ◽

Chromosome 8 ◽

Genome Wide Association Studies ◽

Molecular Genetic Study ◽

Sibling Pairs ◽

Genome Wide ◽

Important Trait ◽

Male Sexual Orientation

AbstractMale 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.

Download Full-text

Genome-wide scan demonstrates significant linkage for male sexual orientation

Psychological Medicine ◽

10.1017/s0033291714002451 ◽

2014 ◽

Vol 45 (7) ◽

pp. 1379-1388 ◽

Cited By ~ 71

Author(s):

A. R. Sanders ◽

E. R. Martin ◽

G. W. Beecham ◽

S. Guo ◽

K. Dawood ◽

...

Keyword(s):

Sexual Orientation ◽

Twin Studies ◽

Pericentromeric Region ◽

Chromosome 8 ◽

Genome Wide ◽

Conflicting Evidence ◽

A Genome ◽

Male Sexual Orientation ◽

Significant Linkage ◽

Genome Wide Scan

BackgroundFindings from family and twin studies support a genetic contribution to the development of sexual orientation in men. However, previous studies have yielded conflicting evidence for linkage to chromosome Xq28.MethodWe conducted a genome-wide linkage scan on 409 independent pairs of homosexual brothers (908 analyzed individuals in 384 families), by far the largest study of its kind to date.ResultsWe identified two regions of linkage: the pericentromeric region on chromosome 8 (maximum two-point LOD = 4.08, maximum multipoint LOD = 2.59), which overlaps with the second strongest region from a previous separate linkage scan of 155 brother pairs; and Xq28 (maximum two-point LOD = 2.99, maximum multipoint LOD = 2.76), which was also implicated in prior research.ConclusionsResults, especially in the context of past studies, support the existence of genes on pericentromeric chromosome 8 and chromosome Xq28 influencing development of male sexual orientation.

Download Full-text

Childhood gender nonconformity and the stability of self-reported sexual orientation from adolescence to young adulthood in a birth cohort.

Developmental Psychology ◽

10.1037/dev0001164 ◽

2021 ◽

Author(s):

Yin Xu ◽

Sam Norton ◽

Qazi Rahman

Keyword(s):

Sexual Orientation ◽

Birth Cohort ◽

Young Adulthood ◽

Gender Nonconformity ◽

Childhood Gender ◽

Childhood Gender Nonconformity ◽

The Stability

Download Full-text

Supplemental Material for Childhood Gender Nonconformity and the Stability of Self-Reported Sexual Orientation From Adolescence to Young Adulthood in a Birth Cohort

Developmental Psychology ◽

10.1037/dev0001164.supp ◽

2021 ◽

Keyword(s):

Sexual Orientation ◽

Birth Cohort ◽

Young Adulthood ◽

Gender Nonconformity ◽

Childhood Gender ◽

Childhood Gender Nonconformity ◽

The Stability

Download Full-text

Multidimensional Assessment of Sexual Orientation and Childhood Gender Nonconformity: Implications for Defining and Classifying Sexual/Affectional Orientations

Journal of LGBT Issues in Counseling ◽

10.1080/15538605.2015.1103676 ◽

2015 ◽

Vol 9 (4) ◽

pp. 240-255 ◽

Cited By ~ 4

Author(s):

Joseph M. Currin ◽

Randolph D. Hubach ◽

Hugh C. Crethar

Keyword(s):

Sexual Orientation ◽

Gender Nonconformity ◽

Multidimensional Assessment ◽

Childhood Gender ◽

Childhood Gender Nonconformity

Download Full-text

“Our World Has Been Rocked”

Trans-Affirmative Parenting ◽

10.18574/nyu/9781479820559.003.0003 ◽

2020 ◽

pp. 69-92

Author(s):

Elizabeth Rahilly

Keyword(s):

Sexual Orientation ◽

Gender Identity ◽

Gender Nonconformity ◽

Gender And Sexuality ◽

Social Constructionist ◽

The Self ◽

Lgbt Rights ◽

Childhood Gender ◽

Childhood Gender Nonconformity ◽

Conceptual Work

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.

Download Full-text

Sexual orientation and childhood gender nonconformity: Evidence from home videos.

Developmental Psychology ◽

10.1037/0012-1649.44.1.46 ◽

2008 ◽

Vol 44 (1) ◽

pp. 46-58 ◽

Cited By ~ 163

Author(s):

Gerulf Rieger ◽

Joan A. W. Linsenmeier ◽

Lorenz Gygax ◽

J. Michael Bailey

Keyword(s):

Sexual Orientation ◽

Gender Nonconformity ◽

Home Videos ◽

Childhood Gender ◽

Childhood Gender Nonconformity

Download Full-text

Does Sexual Orientation Precede Childhood Sexual Abuse? Childhood Gender Nonconformity as a Risk Factor and Instrumental Variable Analysis

Sexual Abuse ◽

10.1177/1079063215618378 ◽

2015 ◽

Vol 29 (8) ◽

pp. 786-802 ◽

Cited By ~ 7

Author(s):

Yin Xu ◽

Yong Zheng

Keyword(s):

Sexual Abuse ◽

Sexual Orientation ◽

Childhood Sexual Abuse ◽

Instrumental Variable ◽

Gender Nonconformity ◽

Gender Nonconforming ◽

Instrumental Variable Analysis ◽

Childhood Gender ◽

Childhood Gender Nonconformity ◽

Variable Analysis

Research suggests that there is a relation between childhood sexual abuse (CSA) and adulthood nonheterosexual orientation. To explore whether nonheterosexual orientation increases the risk of CSA, we recruited a large sample, added the variable of childhood gender nonconformity (CGNC), and applied the instrumental variable method. We found that heterosexual and nonheterosexual men who were more gender nonconforming in childhood were significantly more likely to report having a history of CSA than their gender-conforming counterparts. There was no relation between CSA and CGNC for heterosexual and nonheterosexual women. The instrumental variable analysis revealed that the increased prevalence of CSA experienced by nonheterosexuals compared with heterosexuals may be due to the influence of sexual orientation on CSA. In sum, the results suggest that nonheterosexuality may increase the risk of childhood sexual abuse.

Download Full-text