Gay men have, on average, a greater number of older brothers than do heterosexual men, a well-known finding within sexual science. This finding has been termed the fraternal birth order effect. Strong scientific interest in sexual orientation exists because it is a fundamental human characteristic, and because its origins are often the focal point of considerable social controversy. Our study is a major advance in understanding the origins of sexual orientation in men by providing support for a theorized but previously unexamined biological mechanism—a maternal immune response to a protein important in male fetal brain development—and by beginning to explain one of the most reliable correlates of male homosexuality: older brothers.Abstract
We conducted a direct test of an immunological explanation of the finding that gay men have a greater number of older brothers than do heterosexual men. This explanation posits that some mothers develop antibodies against a Y-linked protein important in male brain development, and that this effect becomes increasingly likely with each male gestation, altering brain structures underlying sexual orientation in their later-born sons. Immune assays targeting two Y-linked proteins important in brain development—protocadherin 11 Y-linked (PCDH11Y) and neuroligin 4 Y-linked (NLGN4Y; isoforms 1 and 2)—were developed. Plasma from mothers of sons, about half of whom had a gay son, along with additional controls (women with no sons, men) was analyzed for male protein-specific antibodies. Results indicated women had significantly higher anti-NLGN4Y levels than men. In addition, after statistically controlling for number of pregnancies, mothers of gay sons, particularly those with older brothers, had significantly higher anti-NLGN4Y levels than did the control samples of women, including mothers of heterosexual sons. The results suggest an association between a maternal immune response to NLGN4Y and subsequent sexual orientation in male offspring.
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