The study clearly links sexual orientation in men with two regions of the human genome that have been implicated before, one on the X chromosome and one on chromosome 8.
The finding is an important contribution to mounting evidence that being gay is biologically determined rather than a lifestyle choice. In some countries, such as Uganda, being gay is still criminalised, and some religious groups believe that gay people can be "treated" to make them straight.
"It erodes the notion that sexual orientation is a choice," says study leader Alan Sanders of the NorthShore Research Institute in Evanston, Illinois.
The region on the X chromosome picked out by the study, called Xq28, was originally identified in 1993 by Dean Hamer of the US National Institutes of Health in Bethesda, Maryland, but attempts to validate the finding since have been mixed. The other region picked out is in the twist in the centre of chromosome 8. Known as 8q12, it was first signposted in 2005.
The latest study involves about three times as many people as the previous largest study, which means it is significantly more statistically robust.
Over the past five years, Sanders has collected blood and saliva samples from 409 pairs of gay brothers, including non-identical twins, from 384 families. This compares, for example, with 40 pairs of brothers recruited for Hamer's study.