The more older brothers a male has from the same mother, the greater the probability he will have a homosexual orientation. Scientists have attributed the effect to a prenatal biological mechanism. The mechanism is thought to be a maternal immune response to male fetuses, whereby antibodies neutralize male Y-proteins thought to play a role in sexual differentiation during development. This would leave some regions of the brain associated with sexual orientation in the 'female typical' arrangement or attracted to men.

Biochemical evidence for this hypothesis was identified in 2017, finding mothers with a gay son, particularly those with older brothers, had heightened levels of antibodies to the NLGN4Y Y-protein than mothers with heterosexual sons.