\Wickelgren, Ingrid. "Discovery of ‘Gay Gene' Questioned," Science 284 (23 April 1999), p.
Six years ago, molecular geneticist Dean Hamer and his colleagues at the National Cancer
Institute (NCI) announced to great fanfare that they had found a genetic link to male
homosexuality. Their work indicated, they said, that an as yet unidentified gene on the X
chromosome influences who develops the trait (Science, 16 July 1993, p. 321). Researchers were
excited by the possibility of one day learning the biological basis for sexual orientation but also
wary, given that initial reports of genetic linkages for other complex traits, such as manic
depression and schizophrenia, had fallen apart under further scrutiny. Now the "gay gene"
linkage man be suffering a similar fate.
On page 665, clinical neurologists George Rice and George Ebers at the University of Western
Ontario in London and their colleagues report failing to find a link between male homosexuality
and Xq28, the chromosomal segment implicated by the NCI team's study. In addition,
unpublished work from a group led by psychiatrist Alan Sanders at the University of Chicago
does not provide strong support for a linkage. Taken together, Rice says, all the results "would
suggest that if there is a linkage it's so weak that it's not important." He adds that genetics may
still contribute to homosexuality, but researchers should be looking elsewhere for the genes.
Hamer disagrees that the Xq28 linkage is weak, citing possible problems with how Rice's team
selected their study subjects. And other observers say that the jury is still out. Elliot Gershon, a
psychiatric geneticist at the University of Chicago, calls the Ontario team's finding "interesting
and important" but cautions that more data are needed. "Failure to find linkage in this study does
not mean it doesn't exist," he says.
That genes may contribute to homosexuality in males became clear in 1991 when psychologist
Michael Bailey of Northwestern University in Evanston, Illinois, found that fully 52% of the
identical twins of gay men were also gay, compared to just 22% percent for fraternal twins. Then
in 1993, Hamer's team pointed to a place where a putative "gay gene" might reside.
They homed in on the X chromosome, which males inherit only from their mothers, because they
noticed a preponderance of gay relatives on the maternal side of the families of the gay men they
studied. When the researchers took a closer look at the X chromosomes of 40 pairs of gay
brothers from the families with maternal gay relatives, they saw that the brothers were far more
likely to share certain DNA signposts, or markers. on the Xq28 region of the chromosome than
would be expected by chance. The team confirmcd the linkage in a second study of 33 new
families with gay brothers, published in Nature Genetics in 1995. In this X chromosome snippet,
the researchers concluded, lay a gene that could nudge males toward homosexuality.
Meanwhile, intrigued by the initial report, Rice and Ebers undertook their own study to see if the
result would hold up. They recruited families with two or more gay brothers through ads in
Canadian gay news magazines. The families responding to the ads included 52 pairs of brothers
willing to donate blood, which the researchers examined for the presence of four markers in
region Xq28, using methods similar to those employed by Hamer's group.
But the Ontario team found that gay brothers were no more likely to share the Xq28 markers than
would be expected by chance. And although a statistical analysis of the data could not rule out
the existence of a gene in this region with a small influence on the trait, it could exclude the
possibility of any gene in Xq28 with a major genetic influence, say, doubling a male's chances of
being gay. Ebers interprets all these results to mean that the X linkage is all but dead. "What is
troubling is that there is no hint or trend in the direction of the initial observation," he says.
Hamer, however, thinks that the way the Ontario researchers selected the families would tend to
hide the Xq28 contribution. He always said, he points out, that the gene does not influence all
cases of male homosexuality but only those that are transmitted maternally And in contrast to his
group, Hamer says, the Ontario team did not select families based on the presence of maternal
transmission. "Maybe there was an X chromosomal linkage in some families, but those families
weren't analyzed," Hamer says.
Ebers says they didn't select their families based on maternal transmission because they found no
convincing evidence for such transmission in the family pedigrees. What's more, even after his
group removed two families that might wash out an X chromosome effect because there were
signs of the trait in females or in the father, the results remained the same. Nor was the effect
evident in a study led by Sanders, which he reported last June at a meeting of the American
Psychiatric Association. His team had found only a weak hint - that wasn't statistically
significant - of an Xq28 linkage among 54 gay brother pairs.
A much larger study, using, say, 200 gay brother pairs, could probably resolve the issue,
researchers say, but limping for such a project has been hard to obtain. So could any successful
efforts to pluck out a gene in Xq28, something Hamer's group is pursuing. But the Ontario team
doubts that route will pay off. "We're looking for a link on other chromosomes," Rice says.