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Genetic regions identified that may relate to male sexual orientation

A recent study conducted at NorthShore University HealthSystem Research Institute has identified regions containing genes that may play a role in male sexual orientation.

In the genome-wide association study (GWAS), the researchers identified two genetic regions with single nucleotide polymorphisms (SNPs) that may be associated with sexual orientation in men.

“Earlier studies, like family and twin studies, have already established that there are some genetic contributions to the trait,” Alan R. Sanders, MD, psychiatrist specializing in behavioral genetics at NorthShore and lead investigator of the study, told Healio Psychiatry. “With the current study, we were trying to extend those studies by trying to locate genes that might contribute.”

Sanders and colleagues evaluated 1,077 homosexual men and 1,231 heterosexual men, all classified by self-report. Most of the homosexual men were participants in a previous linkage study of gay brothers conducted by the NorthShore researchers, and most of the heterosexual men were recruited from a previous nationwide study. They used Affymetrix SNP arrays to genotype and analyze samples collected from the participants.

They identified the most significant cluster of SNPs on chromosome 13 and chromosome 14. The SNPs in these areas may be associated with sexual orientation.

On chromosome 13, the SNPs were identified near SLITRK6, a neurodevelopmental gene expressed primarily in the diencephalon. The diencephalon is a part of the brain that contains an area reported to vary in size in men by sexual orientation.

On chromosome 14, the researchers identified thyroid stimulating hormone receptor (TSHR) genetic variants in intron 1. These variants may account for previous findings that link familial atypical thyroid function and male sexual orientation.

Sanders said although the strongest findings did not achieve genome-wide significance, the study represents the first published GWAS on sexual orientation.

“We’re far from identifying ‘the gay gene’ or anything of that kind,” he said. “A study like this isn’t really designed to establish whether there are genetic contributions. It’s more like it’s a given that there are genetic contributions, and what we’re trying to do is map locations of genes that may be influencing the trait.”

Another intriguing finding was the possible connection between sexual orientation and thyroid function. Sanders discussed information gleaned from a previous study in Denmark, which may be relevant to the findings of the current study.

“For the association signal we found on chromosome 14, it is right at the TSHR gene. Obviously, that’s important for the thyroid, and it’s involved in a type of hyperthyroidism called Graves’ disease,” Sanders said. “When we looked at TSHR and Graves’ disease, we found a large study in Denmark that included same-sex married men. They found that there was a higher rate of Graves’ disease in that group than in their comparison group.”

They also found a potential connection between a phenomenon known as skewed X chromosome inactivation, which has been reported to occur in women with Graves’ disease, and also in mothers of homosexual men.

“That piqued our interest, too,” he said.

Sanders said the findings from the current study are likely to be followed by future studies that will add to the knowledge base in this area.
“This was the first GWAS in the literature on the trait, but I expect that fairly soon, we’ll be followed by other studies on the trait, because we have a whole lot of really large samples that have genetic information,” he said. “And although their focus may not be so much on sexual orientation like our study, these larger genetic studies often have some useful information about sexual orientation that can be leveraged for its study.” – by Jennifer Byrne

Disclosure:  Sanders reports no relevant financial disclosures.