Genome-wide scan demonstrates significant linkage for male sexual orientation

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.

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

Archives of Sexual Behavior ◽

10.1007/s10508-021-02146-x ◽

2021 ◽

Author(s):

Alan R. Sanders ◽

Gary W. Beecham ◽

Shengru Guo ◽

Khytam Dawood ◽

Gerulf Rieger ◽

...

Keyword(s):

Sexual Orientation ◽

Association Study ◽

Gender Nonconformity ◽

Chromosome 8 ◽

Sibling Pairs ◽

Childhood Gender ◽

Genome Wide ◽

A Genome ◽

Childhood Gender Nonconformity ◽

Male Sexual Orientation

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.

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A genome-wide scan of male sexual orientation

Journal of Human Genetics ◽

10.1038/jhg.2009.135 ◽

2010 ◽

Vol 55 (2) ◽

pp. 131-132 ◽

Cited By ~ 16

Author(s):

Sreeram V Ramagopalan ◽

David A Dyment ◽

Lahiru Handunnetthi ◽

George P Rice ◽

George C Ebers

Keyword(s):

Sexual Orientation ◽

Genome Wide ◽

A Genome ◽

Male Sexual Orientation ◽

Genome Wide Scan

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A genome-wide scan shows significant linkage between bipolar disorder and chromosome 12q24.3 and suggestive linkage to chromosomes 1p22–21, 4p16, 6q14–22, 10q26 and 16p13.3

Molecular Psychiatry ◽

10.1038/sj.mp.4001074 ◽

2002 ◽

Vol 7 (7) ◽

pp. 734-744 ◽

Cited By ~ 102

Author(s):

H Ewald ◽

T Flint ◽

T A Kruse ◽

O Mors

Keyword(s):

Bipolar Disorder ◽

Suggestive Linkage ◽

Genome Wide ◽

A Genome ◽

Significant Linkage ◽

Genome Wide Scan

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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.

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