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We're homing in on the pathways that shape sexual orientation - in men, at least. The latest findings reveal genes and antibodies that seem to be part of the complex biology behind homosexuality.

Studies of sexuality have largely tended to focus on men, and for decades there has been evidence that sexual orientation is partly heritable in men. Genetic variations in regions of the X chromosome and chromosome 8 were linked to homosexuality in the mid-1990s, but no specific genes had been found. There was also no explanation for why men are more likely to be gay if they have older brothers, known as the "fraternal birth order effect".

Now, for the first time, two genes that may influence how sexual orientation develops have been identified, while another team's work may explain the fraternal birth order effect.

Alan Sanders at NorthShore University, Illinois, and his colleagues compared DNA from 1077 gay and 1231 straight men. Scanning the men's entire genomes, the team spotted two genes whose variants seem to be linked to sexual orientation (Nature Scientific Reports, doi.org/cg94).

One of the genes sits on chromosome 13. Other research has found that this gene, called SLITRK6, is active in the hypothalamus brain region a few days before male mice fetuses are born. "This is thought to be a crucial time for sexual differentiation in this part of the brain," says neuroscientist Simon LeVay, who in 1991 discovered that hypothalamus size differs between straight and gay men.

The other gene, TSHR, is on chromosome 14 and helps control thyroid function. TSHR function is known to be disrupted in a genetic thyroid condition called Grave's disease, and this disorder is more common in gay men.

Not all men who have these genetic variants will be gay, says Sanders, because many other factors play a role, including the environment. "There are probably multiple genes involved, each with a fairly low effect," he says.

Anthony Bogaert at Brock University, Canada, and his team think that the maternal immune system may also influence sexual orientation.

Our bodies make antibodies to recognise molecules from infectious agents. But pregnant women can sometimes also produce antibodies against fetal molecules - for example, if their fetus has a different blood group. Bogaert's team has found evidence that maternal antibodies may be involved in the fraternal birth order effect.

The team collected blood from 142 women, and screened it for antibodies to a particular brain protein that is made only in males. They thought this would be a good candidate, because it affects how neurons communicate with each other, and it is produced on the surface of brain cells, making it relatively easy for antibodies to find and detect it.

Maternal effect

The mothers of gay sons with older brothers had the highest levels of antibodies against this protein, followed by the mothers of gay sons with no older brothers. Women who had straight sons had less, while women with no sons had the least (PNAS, doi.org/cg93).

The team suggests these antibodies build up in some women's bodies with every male baby they have. At higher concentrations, it is possible that the effect of these antibodies on the protein they target leads to changes in brain development that can have an influence on sexual orientation.

The study was small, so the finding is only preliminary. But it "could pave the way to a detailed understanding of this fascinating aspect of human development", says Dean Hamer at the US National Institutes of Health, who was the first to pinpoint a genetic region linked to homosexuality in 1993.

The genetic finding adds "yet more evidence that sexual orientation is not a 'lifestyle choice'", says Hamer. "But the real significance is that it takes us one step closer to understanding the origins of one of the most fascinating and important features of human beings."