Explanation of fraternal birth order effect on sexual orientation.

A number of studies have by now confirmed that the probability of a boy growing up to be gay increases for each older brother born to the same mother, the so-called fraternal birth order (FBO) effect. Between 15% and 29% of gay men owe their sexual orientation to this effect. Bogaert et al. now present direct biochemical evidence indicating that the increased incidence of homosexuality in males with older brothers results from a progressive immunization of the mother against a male-specific cell-adhesion protein that plays a key role in cell–cell interactions, specifically in the process of synapse formation. Here are the details:

Significance

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.