A preliminary genome-wide association study (GWAS) of male sexual orientation is presented in Scientific Reports this week. Although the findings suggest genetic differences near genes that may have functions associated with sexual orientation, the authors note that potential connections are at best speculative.
Male sexual orientation is multifactorial, with evidence of multiple genetic and environmental contributions. However, genetic association studies for male sexual orientation have been sparse.
Alan Sanders and colleagues conducted a GWAS of male sexual orientation involving 1,077 homosexual men and 1,231 heterosexual men, primarily of European ancestry. The authors detected several regions with multiple single nucleotide polymorphisms (single-letter changes in the DNA), the most prominent of which were located on chromosomes 13 and 14 near genes that have functions plausibly relevant to the development of sexual orientation.
The strongest associated region on chromosome 13 was located between the genes SLITRK6 and SLITRK5. SLITRK6 is a neurodevelopmental gene mostly expressed in a region of the brain called the diencephalon, which contains a region previously reported as differing in size in men depending on their sexual orientation. On chromosome 14, the TSHR (thyroid stimulating hormone receptor) gene spans the region around the most significant single nucleotide polymorphism. Genetic variants in TSHR may conceivably help explain past findings linking atypical thyroid function and male homosexuality.
The authors note that the modest sample size in their study for a trait with complex genetics is a limitation, as is the focus on one ancestral group (European). They note that although the top two association peaks provide interesting and perhaps trait-relevant examples of their closest genes on chromosomes 13 and 14, the potential connections are hypothetical.